About PXE International

PXE About Us

PXE International was founded in 1995 to promote research on and support individuals affected by pseudoxanthoma elasticum (PXE).  We work on behalf of individuals and their families to improve quality of life through advancing research, educating clinicians, and supporting individuals.

PXE International is the prime force in conducting basic and clinical research and providing financial support for applied translational research, product development, and treatment development for Pseudoxanthoma Elasticum (PXE). We steward the intellectual property to equitably advance products and services around the world for the individuals and families living with PXE.

Advocacy Groups as Research Organizations: The PXE International Example

To discover more about the origins of PXE International, watch Sharon Terry's TED talk, or read her articles :  Learning Genetics and Life as a Numerator.

PXE Mission

PXE International

  • Initiates, funds, and conducts research;
  • Provides support for individuals and families affected by pseudoxanthoma elasticum; and
  • Provides resources for healthcare professionals.
PXE Funding

PXE International is a 501(c)(3) not-for-profit organization established in 1995. PXE International research began its funding through private donations. The seeds planted by these small donations have grown into grants from foundations, companies and the government. The success of our activities and our mission as a whole depends on the generosity of you, our supporters.  You can make a tax-deductible donation at any time.

PXE History

 

Patrick and Sharon Terry founded PXE International in 1995 to accelerate research that will result in the treatment of pseudoxanthoma elasticum. PXE International initiates, funds, and conducts research; provides support to affected families; and supports physicians.

 

Initial Plan

Pat was a fire sprinkler designer and Sharon was a former college chaplain when they learned in 1994 that their children (Elizabeth, born 12/12/87, and Ian, born 7/12/89) had PXE. Although they had no formal scientific background, they read medical literature, met with scientists and within two months crafted a comprehensive research plan (Figure 1).
 


Figure 1 - PXE Research Plan
 

The principles of the design are:

  • Fast track all phases of research simultaneously in order to avoid bottlenecks
  • Position the foundation as a firewall between patients and researchers to ensure maximum research participation
  • Initiate, fund, conduct and coordinate research in a central role to maximize efficiency and speed
  • Participate in the national genetics arena to leverage resources otherwise unavailable
  • In all cases, effect change on a systems level so that all diseases benefit 

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Groundwork

The Terrys established PXE International as a 501 (c) (3). They enlisted Dr. Lionel Bercovitch of Brown University as medical director. Dr. Bercovitch is trained in both dermatology and ophthalmology and is selflessly dedicated to long hours of volunteer work for the foundation. A dedicated board and staff provide expertise and assistance.  Except for projects supported by grants from Yardi, the Helmsley Foundation and a few small family foundations over the years, all activities are funded through private donations  Our research meetings have an excellent track record of being funded by NIH grants.

During the first few years, PXE International:

  • Assessed the state of PXE research, including a gap analysis and the funding of small projects in the gap as a way to gather enough data to apply for government and industry grants.
  • Planned a cohesive strategy to avoid overlap and encourage innovative collaborative methods.
  • Established a large registry (see Figure 2) to form the cohort needed for robust studies.
  • Founded the PXE International Registry and BioBank, whose samples now number in the thousands. This lay-managed and -owned bank was the first of its kind in the world and is the model on which the Genetic Alliance Registry and BioBank is founded.

 

Number Affected in PXE International Registry

Figure 2 - Number of Affected in PXE International Registry

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Discovery of the Gene Associated with PXE

The PXE International Blood and Tissue Bank accelerated the discovery of the gene associated with PXE, and Patrick and Sharon Terry participated in the research. In addition to participating in actual wet bench work, they worked to coordinate the activities of a number of laboratories around the world. They were able to get two groups to cooperate, a rare event in the race to find a gene in the 1990's, and the two groups published articles in Nature Genetics. Sharon was a co-author of both articles. As a result of PXE International's material involvement in the discovery, Sharon Terry was listed as a co-inventor on the patent and then assigned her rights to PXE International. The patent issued in the United States in August 2004 and in Canada September 2009. It has been licensed to GeneDx for the diagnostic test.

ABCC6 Gene and Gene Patenting

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Mutation Analysis

PXE International piloted a system to combine the standardization of mutation detection and the input of phenotypic information by placing three dHPLC machines in labs in Belgium and South Africa. Using state-of-the-art informatics, over 100 mutations were discovered and a basis was formed for the development of a diagnostic kit for PXE, which is now available from GeneDx. To date, over 400 mutations have been catalogued. More information on the mutation database

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Diagnostic Kit

PXE International, as part of the federal Collaboration, Education and Test Translation (CETT) program, offers a genetic test for PXE through GeneDx. This is the first diagnostic test for PXE. PXE International has worked to make the test affordable, high quality, with broad access and appropriate genetic counseling. This test helps families understand if siblings of affected individuals have PXE, and may also allow therapies to be targeted to specific mutations determined by the test. 

Shi Y, Terry SF, Terry PF, Bercovitch LG, Gerard GF: Development of a rapid, reliable genetic test for pseudoxanthoma elasticum. J Mol Diagn. 2007 Feb;9(1):105-12. 
Article in PubMed

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Cellular and Molecular Studies

PXE International is funding research in a number of labs studying cell structure and function. One such study includes cytochemical and immunocytochemical localizations, X-ray microanalysis, and confocal microscopy image analysis. This effort will be instrumental in characterizing subcellular organelle behaviors, cellular behavior, and tissue-specific phenotypes.

Another laboratory is conducting cellular protein assay experiments for functional understanding of recombinant protein using the baculovirus insect cell system. This research seeks to characterize the previously observed protein degradation, cellular response to accumulation of unfolded mutant integral membrane proteins in the endoplasmic reticulum, posttranslational modification, and purification of recombinant ABCC6/MRP6 proteins in cells using recombinant baculovirus transfer cell expression plasmids. The purpose of this work is protein purification, targeted peptide design, peptide purification, testing of customized monoclonal antibodies, protein expression characterization, enzymatic functional description, structural dynamic range, and primary functional analysis of wild type and mutant proteins.

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PXE Research Meeting

PXE International coordinated and funded the 2012 PXE Research Meeting, held on September 24-25, 2012 at the Bethesda North Marriott Hotel and Conference Center in suburban DC. This was the fourth international research meeting sponsored by PXE International, and the first completely funded by PXE International. Previous research meetings took place in 1997, 2004 and 2010, supported by NIH grants.

The overall goal of the meeting was to provide a forum for investigators to discuss relevant advances in transporter biology, metabolism, genetics, animal models, biomarker investigations and epidemiology, and for clinically oriented colleagues and PXE International to jointly plan for future research and translational applications. Attendees represented a broad spectrum of individuals with varying expertise including practicing clinicians caring for patients with PXE, physician-scientists and basic science investigators and lay leaders, all of whom share an interest in PXE.

2012 PXE Research Meeting
2010 PXE Research Meeting

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Clinical Trials

With support from the NIH, PXE International continues to plan a clinical trial to examine the effects of multiple treatments for the vision loss caused by PXE. This will take place at the National Institutes of Health (NIH).

During 2013-2014, Dr. Mark Lebwohl and his research team at Mt. Sinai School of Medicine's Dermatology Department in New York are conducting a two-year study of oral magnesium supplementation as an investigational treatment for PXE. The purpose of this study is to evaluate the effectiveness of magnesium oxide supplements on the reversal of calcium deposits in the skin, and the yellow bumps and folds of skin in subjects with pseudoxanthoma elasticum (PXE). Magnesium oxide is a dietary supplement that has been shown in some research to reduce these calcium deposits.

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Conclusion

PXE International is in a unique and powerful position to advocate for individuals affected by PXE, and our work is vital to them and to others facing similar struggles. It is the only hope for many individuals who desperately fear blindness. PXE International is also a role model for many other groups throughout the world.

Despite the now millions of dollars we have placed into service towards PXE research via the NIH, much remains to be done. In the United States, the NIH funds basic research. While this research is critical, we need to move to the next step and look at translating research into treatments. We have a number of labs ready to work on this – it is not only up to us to garner the funds to move forward. It is essential, not only to those affected by PXE but also to other groups, to analyze the incredible gold mine of data we have gathered in our search to understand and meet the challenge of PXE. Working into the wee hours of the morning, our fatigue abates through a burning desire to prevent blindness and other difficulties for the thousands of people on our registry. And in so doing, we are creating a new model of partnership between practitioners, researchers and the individuals they serve. 

PXE Board of Directors

Patrick F. Terry
President
PXE International
Washington, DC
Biography

Lionel G. Bercovitch, MD
Scientific and Medical Director
Brown University
Providence, RI
Biography

Joe Maas, PharmD
Treasurer
J.T.M. Provisions
Harrison, OH
Biography 
A Word from the Board: "Thank God for the PXE community"

Jessica Harper
Los Angeles, CA
Biography
Harper's Corner columns
JessicaHarper.com

Kathy Hersey
Waccabuc, NY
Biography

Ex Officio -
Sharon Terry

Chief Executive Officer
PXE International
Washington, DC
Biography
Curriculum Vitae

Enewsletters
PXE International Registry

You have told us you want answers to your questions about PXE. We want to help you get them, so please contribute your experience with PXE here in our new registry system.

We have partnered with a company called because they are the best at safeguarding your information. Please sign-up or log-in below to share your experiences with, and knowledge of, pseudoxanthoma elasticum. You will also have the opportunity to share your medical record with us in a much easier way for you than mailing them to us!

Please sign-up for a new account even if you were a member of the old PXE Registry.

Learning Genetics

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Originally Printed in Narrative Matters, September / October 2003

 

Finding sparse, uncoordinated research on their children’s rare disease, a couple starts their own organization to jumpstart hopes for the future.

by Sharon F . Terry 

PREFACE: The promise that genetics holds for improving the diagnosis, prevention, and treatment of disease is staggering if not yet fully realized. Such hopes are based on the successful mapping of the human genome and discovery of the genes that mark us for particular maladies—developments that some- day could lead to cures for diseases such as cancer, Alzheimer’s, or diabetes. With this new knowledge and the technology to apply it, however, come questions about what we do with what we know. A host of moral, ethical, and legal uncertainties, at both the pol- icy and personal levels, surrounds the use of genetic technologies. After Sharon Terry dis- covered that her children had a rare genetic disease, she and her husband took a crash course in genetics, founding an organization whose aim is to accelerate research on their children’s condition. Her story reveals the power that proactive parents can wield in expediting research while protecting the privacy of affected families. For all of its potential to cure disease, however, genetic technology also equips us with painful knowledge. Writer Lisa Sweetingham tells us about a couple facing agonizing decisions because of what genetic testing could reveal about their unborn baby’s health.

 

In 1994 we didn’t know a gene from a hubcap. We thought we didn’t need to know. The brave new world of genetics was vaguely interesting but not part of our world—not until our children were diagnosed with a rare genetic condition and we were thrown headlong into a chasm. The chasm was really a threshold. We crossed it, abandoning our ignorance of medical research and clinical treatments for the other side—a desperate need for those systems to per- form exceptionally well. The leap across that threshold took seconds, but learning the realities of these systems was an arduous, eye-opening journey that led us to start a foundation and a new model for accelerating research.

Our children, Elizabeth and Ian, now ages fifteen and thirteen, have pseudoxanthoma elasticum (PXE), a rare genetic condition that causes vision loss, premature wrinkling, and cardiovascular and gastrointestinal disease. The condition’s worst complication is vision loss, devastating people with PXE when they are be- tween thirty and forty.

Two days before Christmas 1994, I brought Elizabeth, then age seven, to a dermatologist. She had small bumps on the sides of her neck that had not disappeared since I had first spotted them a year before. Our pediatrician didn’t think they warranted attention and assumed that my worry was spurred by the recent death of my brother from a brain tumor.

The dermatologist knew immediately that these bumps were a sign of PXE. Glancing at Ian, then five, he said, “Ah, he has it too.” He asked if he could biopsy Elizabeth’s neck and examine her eyes. Confused and terrified, I consented. Why would a dermatologist examine eyes for a skin condition? I learned all too quickly that many skin problems are part of larger, systemic conditions. I also learned that we were fortunate that the dermatologist we chose, who happened to be a neighbor, also happened to be an ophthalmologist. He could do a preliminary assessment of the disease’s effects on my children’s eyes.

 

Distrusting The System

I came home numb and terrified. I called Pat, my husband, desperately wishing he had come to the appointment with us. When you ask our children what they remember from that day and the following weeks, they reply, “The best Christmas ever! We got every toy we asked for!” We recall this period as a time of great fear and confusion as we delved into a morass of medical literature, trying to sort truth from fiction. Popular medical resources such as the Merck Manual described the condition in dire terms, including the possibility that our kids would die at age thirty. What most jarred us was the realization that the research-medical system was not a well-oiled machine. We began to understand

that we could not expect accurate information or a course of treatment.

The only light in the season was our dermatologist, Lionel Bercovitch, who lived a few houses away and knew of our shock and sadness. He suggested we talk about the diagnosis and offered to meet with us at a neighbor’s house, so that our children would not overhear our discussion. And so on Christmas Eve we learned about genes, recessive inheritance, pedigrees, and mutations. The doctor was frank about the limited understanding of the condition. A sense of foreboding began to overlay this already traumatic journey, which was starting to resonate with another experience—my brother’s death.

My brother had died a year earlier of a lethal form of brain cancer, at age thirty-three, leaving behind a young wife and baby daughter. I accompanied my brother and his wife through his diagnosis, treatment, and death. All along the way the doctors treating my brother at a major teaching hospital assured us that he would survive. After his death, I learned that his cancer is always lethal, but there were avenues we didn’t explore because we trusted his doctors to lead us down the right paths.

From this tragedy we found that we needed to be active participants in health care decisions, even to the point of reading the peer-reviewed literature the next time around. We learned that helping loved ones through a health crisis was not like taking a number at the deli counter. If research on PXE wasn’t being done, we couldn’t just wait until they called our number—they might never get to it. So we spent the weeks following our children’s diagnoses in medical school libraries, which aren’t exactly lay-friendly environments. We faced steep learning curves. Pat was a design engineer for a construction company and I was a college chaplain; neither of us had any medical background. We copied every article we could find and brought them home to read, quickly learning that we also would have to in- vest in medical dictionaries; encyclopedias; and biology, genetics, and epidemiology textbooks. Pat poured all of his energy into understanding the science behind the research—his way of coping as a distraught dad. And every glance at the lesions on our kids’ necks renewed our fear.

At the same time, our pediatrician discovered that a researcher at a major university nearby was conducting a research project to find the gene associated with PXE. She contacted the researcher, who came and took samples of our family’s blood. It gave us such hope to think that someone was working on this obscure disease. We were thrilled to participate, even though the researcher provided no informed-consent process. A few days later another researcher called from another major institution and asked for blood samples. We told him to get some from the first researcher. How shocked we were to find that they wouldn’t share and expected us to allow blood to be drawn from small children twice in one week. There was no central repository for the precious blood of people with this rare condition, whose numbers are 1 of every 25,000 Americans. We wondered if this was another indication of the inefficiency of the medical system.

 

Taking The Reins

Pat was relentless —learning the science as quickly as he could and bringing me along. Many nights he would read aloud passages from medical textbooks. We would bat the concepts back and forth, looking them up in medical dictionaries and encyclopedias. Sometimes we’d wake up in the morning to find we had fallen asleep with books and articles strewn around the bed. Some- times we’d fall asleep in tears after viewing photos of sagging skin or reading about the deaths of young people from heart and gastrointestinal complications.

We shielded the kids from this stuff as best we could.

As we waded through the literature, it became obvious that it did not present a clear picture and usually cited case studies that even we, with our limited knowledge, thought were extreme and unrepresentative of the condition. We also noticed that the few studies that included multiple patients contradicted one an- other. Pat’s construction design work relied on project management and coordination; he couldn’t understand why the same principles weren’t applied to medical research. We began to scheme about what we would do if we were man- aging research on this disease. It seemed to us that not only did PXE need a central repository for blood and tissue, it also needed a large cohort of affected people to give researchers a comprehensive understanding of the condition’s manifestations and progression.

We decided to meet with as many authors of PXE peer-reviewed literature as we could. Much to our surprise, everyone we contacted agreed to see us. Their perceptions about the condition ran the gamut, from one researcher who said, “PXE research is a rat hole—no one wants to do it, it isn’t worth it,” to some who were overly optimistic about the results of their efforts. We joined the only sup- port group for the condition and encouraged its founding physician to let us help set up a central registry and sample repository. He was adamantly opposed to both, not wanting to share information with other researchers because he had given much of his professional career to studying PXE. We struggled for several months to work with him, but it became increasingly apparent that his agenda and ours shared little overlap. One long night, Pat and I sat at the dining room table over a bottle of wine and agonized over what we had learned. We could not wait for one researcher to make headway while this disease progressed in our children. From our reading, Pat knew that just as he would coordinate the installation of plumbing and electricity in a building, so should the genetic studies, cell biology, animal models, and other aspects of the research progress on parallel tracks. Although it pained us greatly to do so (we had hoped that all affected people could work together), we started a new advocacy group for PXE. Pat’s skills and mine complemented each other. As he laid the groundwork for the scientific endeavors of the foundation, I began to build the support structure that affected people would need.

We contacted the Washington, D.C.–based Genetic Alliance, the world’s largest coalition of genetic advocacy groups. Its staff mentored us, introduced us to other lay leaders, and helped to focus our activities. With their help we were able to do a great deal in a short time. Gradually the new foundation, PXE International, took more and more of my time. I had been teaching part time and stopped doing anything except establishing the foundation. We enlisted Dr. Bercovitch and met every few nights, so that within six months we had created the PXE International Blood and Tissue Bank, laid the groundwork for an epidemiological study, coordinated dozens of volunteer outreach efforts around the world (from those of a nurse in South Africa to a mom in Romania), and begun to build the PXE International Research Consortium. This process was not easy. Only a combination of the Internet, other support groups, and Dr. Bercovitch’s help made all of this feasible. Our kids began to come to grips with PXE in their own way. Typical of children, they didn’t take it too seriously and instead did things like naming a spider “pseudoxanthoma elasticum,” proud to learn a Latin insect-naming technique!

Elizabeth and Ian have reacted to PXE in a remarkable way. They have skin lesions and the beginning signs of eye disease (although their vision is still fine). They feel most limited by a restriction on contact sports to protect their eyes. They have grown up aware that no one knows much about PXE’s progression but also with ideas about how to fight for a different future. They have testified three times before the House Appropriations Subcommittee on Labor, Health and Hu- man Services, and Education. At age eleven, Elizabeth recommended to the sub- committee that basic research be funded to benefit all conditions, not just hers. They both think that PXE has presented them with opportunities they never would have experienced. They believe that we will make a difference, so they don’t worry too much.

 

Getting Researchers On The Same Page

Watching the disease progress in our children provides us with the incentive to work long hours and craft novel solutions. Our blood and tissue bank is one result of our efforts. The need for such a bank came to us from several different directions: My ever-practical husband knew that we needed a commodity to leverage if we were to have a place at the ta- ble; competing interests of researchers don’t often allow widespread distribution of samples, which can slow research; and we knew that we would be able to offer affected people a centralized bank that would afford them something that they (and we) didn’t have before—confidentiality and anonymity.

Despite everything we had been through, however, new lows were yet to come. Soon after we started the PXE International Blood and Tissue Bank, the researcher in whose lab we banked our samples actively tried to thwart access to the bank by other researchers. We were appalled, maybe naïvely so, that researchers would put their needs for publications, funding, promotions, and tenure ahead of the needs of people living with disease. We apparently experienced an extreme exam- ple of this, but we and other groups have encountered variations of it repeatedly. Fortunately, this problem was counterbalanced by interactions with other re- searchers here and abroad, with whom real collaboration occurred. One of these relationships led to a joint application for the patent on the gene associated with PXE—the first time lay people in an advocacy group have applied for the patent. We consider ourselves stewards of the gene and know that the real issues will be played out in its licensing.

Our foundation sits at the juncture of research, education for affected people, and information for clinicians. We coordinate the PXE International Research Consortium, in which nineteen labs work through us with one another. This al- lows labs to do what they do best—excellent science—while preserving the ability to publish their own discoveries. At the same time, the labs together determine the dates when information sharing will take place. This also lets PXE International see gaps in the plan and make sure that all research phases are simultaneously fast-tracked. For example, we saw that the most difficult aspect for labs was information and sample collection from affected people and their families. In an ever-tightening regulatory climate in which institutional review boards are scrutinizing all human-participant research, our organization provides a firewall between researchers and research participants. This set up protects patient confidentiality and encourages participants’ involvement. It also allows us to re-contact participants when necessary for research while at the same time protecting them. Participants can engage in an unrushed decision-making process with us, deter- mining the risks and benefits of participating in the PXE International Blood and Tissue Bank, the epidemiological study that we sponsor, and other projects. They feel safe, knowing that we are all in the same boat—sharing the distress of living with PXE and searching for options.

 

Consumers As Catalysts

My work with PXE international has taught me that consumers can be central to the research endeavor. We can be a catalyzing force for translating research into the services we desperately need, such as

treatments, technologies to alleviate suffering, and clinical methods of dealing with the conditions. I now serve as president of the Genetic Alliance. This role enables me to work with other groups so that we leverage each other’s capacities to make a difference for our loved ones.

My family’s experience also has showed me that we need strong protections for research participants but not overly onerous regulations that make it impossible for researchers to have access to patients. In the same way that we know that our nation’s health care system needs overhauling, I am convinced that the research process in this country needs to undergo changes that will facilitate collaboration among labs and build large registries that allow discovery of the natural history and progression of disease.

We hope for a treatment that will slow down PXE and spare Elizabeth’s and Ian’s vision, but we know that the advances we seek are usually measured in generations, not lifetimes. For Pat, Elizabeth, Ian, and me, the journey has bonded us together in a profound way. Moreover, I know that when we shoulder our burdens with other advocacy groups, we will help to speed up research that will spare lives. It can’t happen fast enough.

 

Sharon Terry, sterry@pxe.org, is president of the Genetic Alliance and founding executive director of PXE International, a lay advocacy group for the genetic condition pseudoxanthoma elasticum. She is an adviser to the National Institutes of Health’s National Human Genome Research Institute and the Johns Hopkins University Genetics and Public Policy Center.

Life as a numerator: Putting the person in personal genomics

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Life as a numerator: Putting the person in personal genomics

Sharon F. Terry

Genetic Alliance and PXE International, USA

 

1. Introduction

While the science of human genomics is often focused on odds and probability, most of us do not experience risk that way.

I am a carrier of a mutation in ABCC6, as is my husband. Rather than experiencing the odds we would have children with the autosomal recessive condition pseudoxanthoma elasticum (25% each pregnancy) as an abstraction, our reality is having two of two children affected by PXE: our experience is 100%. Twice.

PXE affects 1 in 50,000 people. Our kids are the numerators. In 1994, when PXE was discovered in our then-very-young children, we felt not only overwhelmed by the prospect of taking care of them and anxious about the uncertainty of their futures, but isolated by the rare nature of their condition. Genetics? We didn't want to talk about it then and even if we did, we didn't have anyone with whom we could talk about it.

Today? Not so much. We—and thousands of others in similar circumstances—are bombarded with information from sequencing centers, clinics, research studies, and direct-to-consumer sites. And, spam fatigue notwithstanding, that's mostly to the good. Genetic disease is a long-tail problem that can only be solved if crowdsourcing rises to the occasion, that is, if families like mine and others contributing to and discussed in this issue are not alone. Precision medicine, biomedical re- search, and human health writ large all stand to benefit if the masses get involved. Indeed, I would argue that crowdsourcing is our only hope. Here I describe ways in which this is already happening and a vision for a future where it is standard practice.

 

2. Life on Mars

When our two children were diagnosed with PXE, it felt like we landed on Mars and were being chased by the grim reaper. Fear ripped through us, and no one was speaking words we could understand. This was not just because we could not hear through our fear, but because the world of biomedical research and disease characterization has an in- credibly esoteric and complex vocabulary. Even the sentence structures were complicated — all passive voice and past tense. It was as though the language—and by extension, our family—was not alive anymore.

As if it weren't terrifying enough to enter the stigma-ridden land of The Diagnosed, we immediately discovered an astonishing fact: scientists were not sharing. A few days after our kids' diagnoses, scientists from Harvard came to draw blood from us to use in the search for the causative gene. Two days after that, a separate group of scientists called from the Mt. Sinai Hospital in New York and asked for blood to work on 

PXE gene discovery. When we asked the second set of researchers to ask the first set for blood (and perhaps even collaborate), they expressed amazement that we would ask such a thing! We were struck by how the culture of science, particularly in biomedical research, had so colored the researchers' perspectives that they found our request preposterous. We felt both horrified and hopelessly naive.

But this was only our first foray into a world that left us surprised over and over: a world alien and offensive to us in our need. It seemed that publishing, getting tenure and getting promoted were more important than discovering what was causing PXE. We quickly got over our expectations for a rapid treatment, let alone a cure. What we couldn't get over were the lack of sharing and the intense competition among scientists. Twenty years on we're still not over it.

In 1995 we built a biobank and stored the samples at a major medical center. That was fine until we wanted to share those precious samples beyond that particular university. After notifying the researchers there that we were on our way to the laboratory to take one of 20 stored DNA aliquots per person, each of which we had deposited there our- selves, we arrived to find a lock on the freezer. Many months of arguing ensued, and we finally called the vice president of the medical center. He ordered the release of our samples. We informed the institution that we would be moving the entire collection of hundreds of samples. On the day we arrived to do that, we found the samples on a cart in the hallway — thawed and warm. We also saw that we were missing several aliquots per person. We took our room-temperature samples across town to freezer space we were renting. And then we took our anger and disappointment and channeled them into changing the system.

A few years later, I spent months negotiating the opportunity to do a natural history study of PXE at the National Institutes of Health. I offered to support the salary of a clinician researcher to do the study. Two glaring disconnects emerged. The first related to the study protocol. At this point, I had collected 900 fields of data on 4000 people living with PXE and knew something about its signs, symptoms and progression. But the investigators were adamant that they would focus on measuring phenotypic characteristics that had no correlation to PXE! They discounted our experience and our copious data. Second, they refused to let me be part of the study team. The “offer” was for me to sit in the back of the room; someone even made a joke that I could carry one of the researcher's briefcases. Their excuse for excluding me was that I was not credentialed in biomedical research. Nevermind that I had the equivalent of a PhD in PXE.

These experiences, and dozens of others, fueled a passion in me to lead an organization that was focused on the very people who need their suffering alleviated—one that was less concerned with academic status and more focused on improving the lives of patients and families. I became interested in practical tools that could be applied to any dis- ease or condition, that could help break down silos and enable sharing despite systems and bureaucrats that were and are often obstacles to the outcomes we seek.

Even more critical to me is trying to change the fundamental misalignments embedded in health care and biomedical research. When the President of the United States embraces the rhetoric of patient-and participant-centric research, we can safely say it has reached new heights. Indeed, it was music to my ears to sit in the East Wing in early 2015 and hear Barack Obama say “… I′m proud we have so many patients' rights advocates with us here today. They're not going to be on the sidelines. It's not going to be an afterthought. They'll help us design this initiative from the ground up, making sure that we harness new technologies and opportunities in a responsible way” (Anon., 2015).

As I write this nearly a year later, however, we have yet to see the deep and essential fundamental shift. We are behaving as though we believe that engagement and partnership have value, but we are still not able to articulate that value, and we are not able to tell the truth about the incentives that drive the biomedical research system. I sit in discussions about “patient-centricity” and wonder why the way we keep score remains rooted in tallies of publications and grant monies. I understand that for systems to change to realize beneficial health outcomes requires a long timeline. But I do not apologize for my impatience. Academia, regulators and even many in pharma seem to accept the ideas that: 1) developing drugs requires a decade; and 2) patients are passive data points in this process, i.e., they are to be collected, not consulted.

 

3. Strange attractors

In most of my encounters with the biomedical research system and its recent lust for big data – especially genotype and phenotype data – I′ve found that that those who champion “engagement” often see it as a useful euphemism for recruitment. At one level I understand this: I do not advocate for engagement for engagement's sake. But neither do I reduce it to a top-down call for increased sample size at all costs.

I think that this new intense interest in engagement, participation, and partnership is what chaos theorists David Ruelle and Floris Takens would call a “strange attractor” (Ruelle and Takens, 1971). The definition describes “basins of attraction within the system that lure the system into a new pattern of activity.” Engagement and participation, I hope and expect, will recenter the system and create authentic partnerships. Individuals, families and communities will take their rightful place as co-designers of new ways of engaging with their health.

In this regard, I am all in on an experiment. Together with Private Access, an innovative technology company, Genetic Alliance has built the Platform for Engaging Everyone Responsibly (PEER). It shifts the center of attention away from institutions, researchers, and even advocacy organizations, and toward individuals. Using PEER, each individual makes choices about data sharing, privacy, and access in a granular and dynamic way. It is our firm belief (and we have invited researchers to study this hypothesis) that if people make these choices for themselves, they will drive the market. They will aggregate themselves not in disease silos, but in pathways, phenotypes and symptoms that they strongly feel need attention and to which they are prepared to commit.

How does PEER work? In one example, we engaged with five sickle cell advocacy organizations and were able to learn from individuals living with sickle cell what mattered to them, and to deliver this information, along with patients' associated socioeconomic data, to the Food and Drug Administration for its Patient-Focused Drug Development program. We therefore extended the reach of the FDA's program to individuals who couldn't travel to metro DC to attend a hearing, or who were not able to post to the docket (the special web-based system that the government uses to catalog public comments).

In another example that is ongoing, ten disease advocacy organizations are working together in a boundary-free way to use the health information they collect across 15 diseases encompassing seemingly unrelated common (e.g., hepatitis, breast cancer) and rare (e.g., dyskeratosis congenita, Joubert syndrome) conditions. As a part of PCORnet, the national clinical research network being created by the Patient Centered Outcomes Research Institute (PCORI), these organizations are working to define research priorities and advance them together. This example is just one of 20 Patient-Powered Research Networks (PPRN) in PCORI that seek to run dozens of experiments on what constitutes true participant-centric research, how to build a network that will shift the current paradigm, and how to develop more robust strange attractors, all while measuring their impact on the current research and services system.

Plenty of obstacles and challenges to these sorts of approaches remain. Large-scale research on human beings is a young pursuit. And formal governance of it is even younger. Most of the same incentives that kept researchers from sharing samples and data in 1994 are still in place. And while patient-and participant-advocates are more frequently invited to discussions surrounding research initiatives, we are still routinely marginalized: we have a seat at the table but rarely do we get to have any meaningful say about what's on the menu or who should be invited to the meal. I hear rhetoric calling for “bridging to ‘those’ people” and “inviting them in.” But to my ears those terms are harsh and grating: they perpetuate an “us” and a “them.” We are all us and we are all them.

 

4. Street cred

The “us and them” frame is more than a linguistic peeve. In recent years, those of us who have been at this for a while have found our legitimacy called into question. There are those, even within the patient and participant advocacy movements, who now routinely discount what some of us do. Some claim that we are not ‘true patients’ because we have peer-reviewed papers, conduct research, lead large organizations and/or work to influence policy at multiple levels—we are “them.” In ways that I find both saddening and ironic, it seems that our very efforts have somehow sowed distrust. We are suddenly written off as having Stockholm syndrome or not truly representing patients.

More than any slight from a researcher ever could, hearing this from fellow advocates hurts. I am still, first and foremost, mother to my two children who live with a genetic condition. I would much rather my family not live life as a numerator, but I—like all families coping with any of the thousands of serious health conditions, be they common or rare—have no choice. All we can do is fight.

Meanwhile, my daughter has succeeded me as the executive director of PXE International. She has doubled the organizational budget and doubled the number of affected individuals enrolled in two short years. Her mission, like mine, remains unchanged: it is not to have a scientific career or access to power, but to alleviate suffering—her own, her brother's, and the thousands like them.

When we have done that for the larger community of numerators, we will gladly shut off the lights and go home.  

 

References

Anon., 2015. President Barack Obama's speech on the precision medicine initiative. http://www.whitehouse.gov/photos-and-video/video/2015/01/30/president-obama-speaks-precision-medicine-initiative (30 January).

Ruelle, D., Takens, F., 1971. On the nature of turbulence. Commun. Math. Phys. 20 (3), 167–192.

Barbara Drewicz

Barb is a native of Southeastern Pennsylvania where she currently resides with her husband, Mark. She has two adult daughters and four grandchildren. She graduated from West Chester University with a BA in Psychology and an M.Ed in School Counseling. 

She has had a long and rewarding career in the Human Services field in both private and public sectors, more recently in the public education system serving for over 25 years as lead primary school counselor and coordinator.  She has served as Board Secretary and County representative with the Pennsylvania School Counselor Association for over twenty years, retiring in 2014.

First and foremost she is the mother of a daughter with PXE, which is the genesis of her connection to PXE International.  Since her daughter was first diagnosed in 2001, she and her family have been on a journey to educate & inform themselves with the most accurate, research-based information about this unique and challenging condition.  Finding both knowledge and support within this organization fulfilled a need to both help her daughter and contribute through volunteering. 

Since being on the board, Barbara has had the opportunity to speak with many PXErs and has been continually inspired by this community’s positivity, optimism and personal stories of fortitude in the face of their daily challenges.  Likewise, she feels the integrity, dedication and hard work of the shoe-string PXE staff and its leaders, challenges us all to do more to help pursue its mission of research in pursuit of treatment and cure to end the burden of PXE in our world.

Jessica Harper

Actress, Singer, Songwriter, Author
Los Angeles, CA

 

Jessica Harper lives in Los Angeles and New York. She is married to Tom Rothman and has two grown daughters, Elizabeth and Nora. As an actress Jessica has co-starred in films such as Stardust Memories with Woody Allen, Pennies from Heaven with Steve Martin, My Favorite Year with Peter O'Toole and Minority Report with Tom Cruise. She has appeared in numerous TV shows, including AppleTV’s new series, See, and the upcoming FX series, The Old Man. Her extensive theatrical credits range from Hair on Broadway to American Anthems with Al Pacino, at the Long Wharf Theater.

As a musical artist, Jessica has written and produced seven albums of music for children. As an author, she penned a dozen children’s books, including the LA Times bestseller, Nora’s Room. She also wrote The Crabby Cook Cookbook for Workman Publishing. In addition, she wrote, produced, and narrated Winnetka, a memoir/podcast, which debuted last year.

Jessica and her brother Sam were diagnosed with PXE as children. Sam’s twin brother Charlie was diagnosed in his fifties. Jessica's first contact with PXE International was through the website several years ago. The Amsler grid provided in the MemberGram helped her detect changes in her vision. Her UCLA doctor suggested she contact Sharon Terry and get involved in the organization. She attended the conference in Oakland in 2002. She was impressed with the drive, commitment and intelligence of Pat and Sharon, and was glad to accept when asked to join the board. Since then she has worked to support the board and PXE International through fundraising in the Hollywood community and beyond.

 

To learn more about Jessica's children's books and music, visit Jessica's website.

Joe Maas

Treasurer, PXE International
JTM Provisions, Harrison, OH

 

 Joe Maas was born and raised in Cincinnati, Ohio where he continues to live today.

Joe is married to Robin and has three grown children, two sons and a daughter. He attended the University of Cincinnati in Ohio and received a BA in pharmacology. Although he is a licensed pharmacist in Ohio, he has not worked in the field since 1998. He now helps to run a very successful food processing business he owns with his three brothers.

In 1999 his son Kevin was diagnosed with pseudoxanthoma elasticum (PXE). An Internet search on the subject brought up PXE International, which he contacted immediately. During the first days, as he came to terms with the diagnosis, he spoke to Pat and Sharon Terry several times. It helped to speak to other parents in the same situation. He joined the foundation and attended the conference in Boston in June 2000. His involvement included financial support and keeping up with current information. While attending the conference in Oakland, CA in 2002, he was flattered when Sharon asked him to join the board.

His vision for the board is to continue to search for a treatment for PXE. His medical education background allows him to follow trial studies and understand the technical terminology used in their reports. This skill will allow him to evaluate the proposed medical studies and help to direct the funds available for research. He is excited about the studies being conducted and is hopeful that a treatment will be found soon. He is also proud to be a part of PXE International because of their work concerning the moral issues surrounding genetic research. He can appreciate the importance of a patient´s privacy and supports PXE International taking a stand to foster political policy regarding how genetic information is handled.

Through his association with PXE International and the Terrys, Joe has come to understand that his responsibilities extend beyond his own child. He recognizes his role on the board is to help people who are currently affected with the symptoms of PXE, and those yet to come.

Joe also serves on the boards of several charitable entities in the Cincinnati area as well as the boards of several food industry organizations.

Kathy Hersey

Kathy Hersey was born and raised in Garden City, NY and now resides in Westchester County, NY. She is married to Robert and has three sons, Rob, Austin and Jonathan. Kathy's son Rob was diagnosed with PXE around 1996. The Hersey's met the Terry's shortly after Sharon and Pat founded PXE International. It was so relieving to find such great support with such an isolating disease. PXE International has grown over the years and we have met so many wonderful people. PXE International has become like a second family to us.

Kathy and Robert became grandparents in October 2018. Rob and his wife Christine welcomed their first child James Hersey. He brings the whole family so much joy.

With the help of Kathy's family and the Wall Street community, fundraising efforts began. Since 2000, Kathy's brother Joe and his band, The Rockbrokers, have raised money for PXE International in the U.S. and abroad, donating $650,000. The Rockbrokers played at the PXE International 15th anniversary conference in Washington D.C. in September 2010.

Kathy hopes to continue to support the board, and looks forward to new and exciting research coming from PXE International.

Lionel Bercovitch, MD

Scientific and Medical Chair, PXE International
Professor of Dermatology, Brown Medical School, Providence, RI

 

Dr. Lionel Bercovitch, the founding medical director of PXE International, is uniquely qualified as an advocate, clinician, and researcher for PXE. He became intensely involved in PXE following his diagnosis of Elizabeth and Ian Terry with the disorder in 1994. Since then, he has authored many papers on PXE, examined hundreds of people affected by PXE, some of whom have come from all over the US and as far away as South America and Australia for second opinions,  and given much of his spare time to research on the condition. He does comprehensive clinical evaluations of PXEers, has been actively involved in many clinical research projects, and is a clinical resource for healthcare professionals and laypersons alike.

Dr. Bercovitch is Professor of Dermatology at Warren Alpert Medical School of Brown University, Providence, RI, and serves as Director of Pediatric Dermatology at Hasbro Children's Hospital, also in Providence. He is Co-Editor-in-Chief of Pediatric Dermatology. He is also heavily involved in bioethics education for dermatology residents.

Dr. Bercovitch is a graduate of the University of Manitoba Medical School in Canada, is board certified (US) in Dermatology, Pediatric Dermatology and Internal Medicine, and is a Fellow of the Royal College of Surgeons of Canada in Ophthalmology.

 

Webinars

 

Presentations at the 2012 Biennial Conference and Prior 

  • Plenary Address
  • Women's Issues in PXE
  • General Q & A

 

Areas of Interest

Genetics of PXEPXE and the MetabolismClinical ManifestationsEpidemiology of PXEClinical Trials

 

Publications

Uitto J, Váradi A, Bercovitch L, Terry PF, Terry SF. Pseudoxanthoma elasticum: Progress in research toward treatment: Summary of the 2012 PXE International research meeting. J Invest Dermatol. 2013 Jun;133(6):1444-9.Lay summaryFree article at Journal Website. PMID: 23673496

 

Wang AR, Fonder MA, Telang GH, Bercovitch L, Robinson-Bostom L. Late-onset focal dermal elastosis: An uncommon mimicker of pseudoxanthoma elasticum. J Cutan Pathol. 2012 Oct;39(10):957-61. PMID: 22882354

 

Uitto J, Bercovitch L, Terry SF, Terry PF. Pseudoxanthoma elasticum: Progress in diagnostics and research towards treatment: Summary of the 2010 PXE International Research Meeting. Am J Med Genet A. 2011 Jul;155A(7):1517-26. Lay summaryFree article in PubMed. PMID: 21671388

 

Bercovitch L, Martin L, Chassaing N, Heffron TW, Bessis D, Vanakker V, Terry SF. Acquired pseudoxanthoma elasticum presenting after liver transplantation. J Am Acad Dermatol. 2011 May;64(5):873-8. Lay summaryFree article in PubMed. PMID: 21397982

 

Ramsay M, Greenberg T, Lombard Z, Labrum R, Lubbe S, Aron S, Marais AS, Terry S, Bercovitch L, Viljoen D. Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals. J Dermatol Sci. 2009 Jun;(54)3:198-204. PMID: 19339160

 

Garcia-Fernandez MI, Gheduzzi D, Boraldi F, Paolinelli CD, Sanchez P, Valdivielso P, Morilla MJ, Quaglino D, Guerra D, Casolari S, Bercovitch L, Pasquali-Ronchetti I. Parameters of oxidative stress are present in the circulation of PXE patients. Biochim Biophys Acta. 2008 Jul-Aug;1782(7-8):474-81. PMID: 18513494

 

Vanakker OM, Leroy BP, Coucke P, Bercovitch LG, Uitto J, Viljoen D, Terry SF, Van Acker P, Matthys D, Loeys B, De Paepe A. Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. Hum Mutat. 2008 Jan;29(1):205. Free article at Journal Website. PMID: 18157818

 

Pfendner EG, Vanakker OM, Terry SF, Vourthis S, McAndrew PE, McClain MR, Fratta S, Marais AS, Hariri S, Coucke PJ, Ramsay M, Viljoen D, Terry PF, De Paepe A, Uitto J, Bercovitch LG. Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. J Med Genet. 2007 Oct;44(10):621-8. Free article in PubMedPatient Summary. PMID: 17617515

 

Shi Y, Terry SF, Terry PF, Bercovitch LG, Gerard GF. Development of a rapid, reliable genetic test for pseudoxanthoma elasticum. J Mol Diagn. 2007 Feb;9(1):105-12. Free article in PubMed. PMID: 17251343

 

Terry SF, Terry PF, Rauen KA, Uitto J, Bercovitch LG. Advocacy groups as research organizations: the PXE International example. Nat Rev Genet. 2007 Feb;8(2):157-64.  Free article. PMID: 17230202

 

Bercovitch RS, Januario JA, Terry SF, Boekelheide K, Podis AD, Dupuy DE, Bercovitch LG. Testicular microlithiasis in association with pseudoxanthoma elasticum. Radiology. 2005 Nov;237(2):550-4. Free article at journal websitePatient SummaryPoster: Testicular Microlithiasis in PXE. PMID: 16244264

 

Bercovitch L, Leroux T, Terry S, Weinstock MA. Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum. Br J Dermatol. 2004 Nov;151(5):1011-8. Journal articlePatient Summary. PMID: 15541079

 

Bercovitch L, Terry P. Pseudoxanthoma elasticum (2004). J Am Acad Dermatol. 2004 Jul;51(1 Suppl):S13-4. Review. PMID: 15243491

 

Gheduzzi D, Sammarco R, Quaglino D, Bercovitch L, Terry S, Taylor W, Ronchetti IP. Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum. Ultrastruct Pathol. 2003 Nov-Dec;27(6):375-84. PMID: 14660276

 

Bercovitch L, Robinson-Bostom L, Terry SF, Pasquali-Ronchetti I, Harrist T. Re: yellowish papules on flexural areas in a child. Pediatr Dermatol. 2003 Nov-Dec;20(6):543-5; author reply 545. PMID: 14651582

 

Lebwohl M, Lebwohl E, Bercovitch L. Prominent mental (chin) crease: a new sign of pseudoxanthoma elasticum.J Am Acad Dermatol. 2003 Apr;48(4):620-2. Patient Summary. PMID: 12664032

 

Bercovitch L, Schepps B, Koelliker S, Magro C, Terry S, Lebwohl M. Mammographic findings in pseudoxanthoma elasticum. J Am Acad Dermatol. 2003 Mar;48(3):359-66. Patient Summary. PMID: 12637915

 

Le Saux O, Beck K, Sachsinger C, Treiber C, Göring HH, Curry K, Johnson EW, Bercovitch L, Marais AS, Terry SF, Viljoen DL, Boyd CD. Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa. Hum Genet. 2002 Oct;111(4-5):331-8. PMID: 12384774

 

Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD. A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. Am J Hum Genet. 2001 Oct;69(4):749-64. Free article in PubMed. PMID: 11536079

 

Gheduzzi D, Taparelli F, Quaglino D Jr, Di Rico C, Bercovitch L, Terry S, Singer DB, Pasquali-Ronchetti I. The placenta in pseudoxanthoma elasticum: clinical, structural and immunochemical study. Placenta. 2001 Jul;22(6):580-90. Download the PDF of this article. PMID: 11440547

 

Terry SF, Bercovitch L, Boyd C (June 2001) Pseudoxanthoma elasticum (PXE). In: GeneClinics: Clinical Genetic Information Resource [database online]. Copyright, University of Washington, Seattle. Available at http://www.geneclinics.org. PMID: 20301292

 

Sherer DW, Bercovitch L, Lebwohl M. Pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring. J Am Acad Dermatol. 2001 Mar;44(3):534-7. PMID: 11209132

 

Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, Pasquali-Ronchetti I, Pope FM, Richards A, Terry S, Bercovitch L, de Paepe A, Boyd CD. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. 2000 Jun;25(2):223-7. PMID: 10835642

 

Le Saux O, Urban Z, Göring HH, Csiszar K, Pope FM, Richards A, Pasquali-Ronchetti I, Terry S, Bercovitch L, Lebwohl MG, Breuning M, van den Berg P, Kornet L, Doggett N, Ott J, de Jong PT, Bergen AA, Boyd CD. Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16. Genomics. 1999 Nov 15;62(1):1-10. PMID: 10585762

Sharon Terry, MA

Chief Executive Officer, PXE International

View my TEDMED talk

 

As ‘just a Mom’ with a master’s degree in Theology, she cofounded PXE International, a research advocacy organization for the genetic condition pseudoxanthoma elasticum (PXE), in response to the diagnosis of PXE in her two children in 1994.  She is a co-discoverer of the ABCC6 gene, and patented it to ensure ethical stewardship in 2000, assigning her rights to the foundation.  She subsequently developed a diagnostic test and conducts clinical trials.  She is the author of 150 peer-reviewed papers, of which 30 are clinical PXE studies. Her story is the topic of her TED Talk and TED Radio Hour.

She is also President and CEO of Genetic Alliance, an enterprise engaging individuals, families and communities to transform health.  Genetic Alliance works to provide programs, products and tools for ordinary people to take charge of their health and to further biomedical research.

In her focus at the forefront of consumer participation in genetic research, services and policy, she serves in a leadership role on many of the major international and national organizations, including the Precision Medicine Initiative Cohort Advisory Panel; Accelerating Medicines Partnership; National Academy of Medicine Roundtable on Genomics and Precision Health; the PhenX scientific advisory board; the Global Alliance for Genomics and Health; the International Rare Disease Research Consortium Executive Committee; Genome Medical; LunaDNA; and as Founding President of EspeRare Foundation of Geneva, Switzerland. Terry is co-founder of the Genetic Alliance Registry and Biobank.  She is on the editorial boards of several journals, including Genome, Patient Engagement Editor for Genetic Alliance’s official journal Genetic Testing and Molecular Biomarkers, Chief Patient Advisor for Clinical and Translational Science. She led the coalition that was instrumental in the passage of the Genetic Information Nondiscrimination Act.  She received an honorary doctorate from Iona College for her community engagement work in 2006; the 2011 Research!America Distinguished Organization Advocacy Award and an inaugural member of Disruptive Women in Health Care in 2009; and the Clinical Research Forum and Foundation’s Annual Award for Leadership in Public Advocacy in 2011. She was named one of FDA’s “30 Heroes for the Thirtieth Anniversary of the Orphan Drug Act” in 2013. She is co-inventor of the Platform for Engaging Everyone Responsibly (PEER), receiving a large grant from the Robert Wood Johnson Foundation in 2014.  PEER undergirds the Community Engaged Network for All (CENA), a PCORnet member since 2013. She is Co-PI of the PCORnet Coordinating Center and Chair of the PCORnet Engagement Committee. She was a member of the Blue Ribbon Panel’s Working Group on Enhanced Data Sharing for the Cancer Moonshot. She was named a National Associate of the National Research Council, National Academies of Engineering, Sciences, and Medicine for her extraordinary service. She received the Health 2.0 Health Activist award in 2016. In 2017, she co-founded the People Centered Research Foundation. In 2019, she won the Luminary Award from the Precision Medicine World Conference.

Terry is an Ashoka Fellow.  She is an avid student and facilitator of Gestalt Awareness Practice, offering workshops and individual facilitation. Her daughter and son are why she started down this path. They, their wives, and her granddaughter ground and enliven her.

Patrick Terry

President, PXE International

 

Patrick Terry brings the wisdom of a perspective forged from personal experience and extensive work in the lay advocacy (patient) community. Following the diagnosis of their two children with a rare condition, pseudoxanthoma elasticum (PXE) in 1995, Patrick and his wife, Sharon, founded PXE International, a dynamic lay organization that initiates, coordinates and funds research, as well as worldwide patient support. In the years since, PXE International has grown to include an international 19 lab consortium, 52 support offices worldwide, a private blood and tissue bank, and a database registry of thousands of affected individuals. The culmination of his effort toward global coordination of research has led to tremendous scientific advances for PXE and related diseases.

Patrick has worked with many professional medical organizations, and is on the professional advisory board of the Genetic Alliance of Washington, DC. His participation in biomedical research in our nation's capital has been instrumental in the overall increased funding for the NIH as well as recognition of the power and importance of lay advocacy groups. In all of his work he has emphasized the importance of the consumer as a full and active partner in the collaborative process of genomics research and healthcare services. His vision for creating a new paradigm for empowering consumer involvement in research has not only been brought to fruition in the success of PXE International, but has been embodied in mentoring many other lay advocacy organizations.

Patrick is a social entrepreneur who has founded a series of innovative philanthropic, research, and commercial organizations based on the life sciences, applied technology, and social-network theory. He is the co-founder of Genomic Health [NASDAQ: GHDX], and former Director at the pioneering personalized medicine company based in California. He is a lay person – his scientific, technical, and medical knowledge is all self-taught. He has published dozens of peer-reviewed scientific papers, articles, and book chapters in the fields of genetics, translational research, and personalized medicine. Some of his past activities included leadership positions on numerous trade associations, professional societies, corporate boards, and federal advisory bodies. He has experience doing hands-on bench science, coordinating human genetics research, conducting basic research on rare diseases, and managing a life sciences patent portfolio. He has received many honors and awards in the business and scientific communities in the U.S. and internationally. He has dedicated his career to helping people and advancing a patient-centered perspective in research, product development, and translational medicine.

Patrick has also founded the following organizations: Personalized Medicine Coalition, 21st Century Medicine Coalition, Genomic Health, Genetic Alliance BioBank, Technic Solutions, International Genetic Alliance, BioLogos Foundation, and Grand Therapeutics.

Patrick now works as Chief Commercial Officer at Claritas Genomics in Boston, Massachusetts.
 

Webinars

Presentations at the 2010 Biennial Conference and Prior

2010 Annual Report

View As PDF

Logo

 

2010 Annual Report

4301 Connecticut Ave, NW

Suite 404

Washington, DC 20008

http://www.pxe.org

info@pxe.org

202.362.9599

 

Mission Statement

PXE International initiates, conducts and funds research on pseudoxanthoma elasticum (PXE), educates clinicians and supports affected individuals.  

 

Introduction

Strategic visioning and new leadership resulted in effective advances in patient education/information and research in 2010. Our concrete and measurable goals, established in preparation for the next 10 years, strive to increase connectivity with our participants, productivity and effectiveness of this essential support system for individuals affected by pseudoxanthoma elasticum (PXE). PXE affects one in 50,000 to 100,000 people. Though these numbers are small (resulting in about 4100 individuals from around the world in our registry), service to these individuals is as critical as it is for any disease. In fact, PXE International often serves as a model for other conditions and their research and services.

Through listservs, webinars, MemberGrams, updated print information, eNewsletters and social media (Twitter, Facebook, LinkedIn), we have been able to increase our communications with patients and their families as well as further understand our changing community. We have also built a better mechanism for communicating with researchers to keep them informed of opportunities and developments in their arenas.

In the last year, PXE International has been able to transform our processes, branding, and products. This was possible with generous grants from foundations such as the Leona M. and Harry B. Helmsley Charitable Trust and Yardi Systems, as well as thousands of individual donations.

PXE International completed its 15th year of advocacy, research, and support. We have come a long way from the children’s’ playroom in which we were founded. So has our community. Our population is changing and growing and requiring different services than it did before. We must step into the 21st century and take full advantage of the exciting new methods of communication and information dissemination. Extensive strategic planning, including new, dynamic leadership catalyzed our achievements this past year.

 

PXE Research

One of PXE International’s major goals is to support and facilitate research. This is a very expensive pursuit and requires that we vigorously commit our time, energy and resources for the discovery of new information and treatments. This year we launched a 15th Anniversary Challenge with the bold goal of raising $1.5 million over the next 5 years.

 

Fig1
Pledges as of January 2011: $300,000

 

A Selection of 2010 Accomplishments

Projects

  • Created a listserv and regular communication mechanism for the Research Consortium Updated all email addresses on the listservs

  • Updated all of the addresses in the database through an online and a phone campaign

  • Codified processes for conducting webinars, planning a biennial conference, planning a research conference and producing a MemberGram

  • Created new website with fresh design, new content, and better content management system

  • Rebranded Organization

  • Planned and held the 6th Biennial Conference and the 2010 Research meeting

  • Produced and distributed two Membergrams and 6 eNewsletters

  • Organized and held 6 educational webinars

 

Goals for 2011

Projects

  • Plan and hold 4-­‐6 international and regional meetings

  • Publish eNewsletter monthly

  • Publish two supplemental updates in spring and summer and one (1) Membergram in November

  • Create and implement outreach program to engage existing community and generate more members and funds

  • Raise at least 1/5th of our Anniversary Challenge

  • Actively pursue and promote research opportunities with grants and reward incentives

  • Create fundraising committee

  • Provide support to those seeking to organize and hold fundraisers

  • Use our social media in a more effective and professional way (Twitter, Facebook)

  • Make our website functional, attractive, and efficient

  • Revise all other medical bulletins as well as update the FAQ area

  • Pursue research into PXE biomarkers, substrate, organ transplantation in mouse model, and developing a clinical trial

  • Explore and raise funds to hire a research director

2011 Annual Report

View As PDF

Logo

 

2011 Annual Report

4301 Connecticut Ave, NW

Suite 404

Washington, DC 20008

http://www.pxe.org

info@pxe.org

202.362.9599

 

Mission Statement

PXE International initiates, conducts and funds research on pseudoxanthoma elasticum (PXE), educates clinicians and supports affected individuals.

 

Introduction

PXE International has had an incredible year. Now completing our 16th year of existence, we are constantly on the road toward a treatment for this condition. With exciting developments in drug research there is the very real chance that a child diagnosed today would never face the reality of vision loss, and those with symptoms have already been able to mitigate the worst outcomes. This is the most exciting time in our organization’s history since we found the gene in 2000. Along with this exciting new research, we have also increased our patient support network holding six regional meetings in four countries in 2011. This coming year we will be holding our professional research meeting as well as our 9th Biennial Patient Conference in September of 2012.

One of the roadblocks toward access to treatment is the cost of further research. As it currently stands, it would cost around 2.5 million dollars to fund all the areas of interest that our collaborating scientists have proposed. Grant requests are submitted to us often and we are faced with the difficult choice of where to place our limited funds.

With the economy lagging, funding for rare disease research is difficult and sometimes impossible to find. Public and private agencies have begun prioritizing their missions and often smaller organizations and disease groups drop off the list. This leaves the personal connections we all have to each other. Funding multimillion-­‐ dollar scientific research from donations of $2, $5, $20, and even $500 is a daunting task. But with your amazing generosity, and whatever you have found in your hearts to give, we have come an incredible distance.

It has always been the task of the few to fight the good fight. We at PXE International champion every individual who visits our donation page, writes a check, donates their medical records or fills out an online questionnaire in our Epidemiological Study. Each one of those actions moves us closer to our collective goal to make living with PXE an experience free of hardship.

 

PXE Research

Last year we announced our intention to raise 1.5 million dollars for research in just 5 years – the 15th Anniversary Challenge. We knew it would be a tough mission to complete. Now we are just over a year into the challenge and that means it would be great if we could have raised 1/5th of the challenge goal. Together with us, you have all raised over $450,000! An amazing feat and almost 1/3rd of the entire amount. This is a testament to the unending support of the wonderful people who suffer daily at the hands of this disorder. Let’s not stop now! We must keep the momentum going and make sure we can truly invest in the best science and research possible around the world.

 

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2011 Accomplishments

  • Completed rebranding of organization in print and online with new logo and website
  • Increased the level of activity and awareness by utilizing social media and a more comprehensive website
  • Held regional meetings in four countries
  • Published two MicroMemberGrams and one Fall MemberGram
  • Raised almost 1/3rd of our anniversary challenge – ahead of schedule!
  • Conducted the beginnings of our massive Epidemiological Study

2012 Goals

  • Hold more regional meetings around the world
  • Publish MicroMemberGrams, MemberGrams, eNews, Webinars, and other media
  • Increase our international presence and resource lists
  • Plan and conduct two back-to-back conferences
  • Fundraise and fund as much research as possible
2012 Annual Report

View As PDF

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2012 Annual Report

4301 Connecticut Ave, NW

Suite 404

Washington, DC 20008

http://www.pxe.org

info@pxe.org

202.362.9599

 

Mission Statement

PXE International initiates, funds and conducts research on pseudoxanthoma elasticum (PXE), provides support for individuals and families affected by PXE, and provides resources for healthcare professionals.

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Introduction

PXE International, founded in 1995, is the prime force in basic and clinical research on pseudoxanthoma elasticum (PXE). We provide financial support for applied translational research, product development, and treatment development for PXE. We steward the intellectual property associated with the ABCC6 gene to equitably advance products and services around the world for the individuals and families living with PXE. We work with other disease organizations to pilot new and better ways of educating researchers, clinicians and individuals interested in PXE.

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PXE Research

Major discoveries

2012 was an important year for pseudoxanthoma elasticum research. Major discoveries included:

  1. Magnesium may have a substantial impact on mineralization in soft tissue of those affected by PXE. Studies conducted on mouse models of PXE found that decreasing dietary magnesium increased mineralization of soft tissue1. In contrast, increasing dietary magnesium in mouse models of PXE decreased mineralization of soft tissue2. In humans, this means that magnesium may be an effective treatment for PXE. For a lay summary of this research, go to http://pxe.org/restricting-­‐dietary-­‐magnesium-­‐ accelerates-­‐mineralization-­‐PXE-­‐mouseImg3
  2. After a two-­‐year study, Avastin and Lucentis were determined to be equally effective in treating age-­‐related macular degeneration (AMD)3. While AMD is not the same as PXE, these treatments are often used to combat PXE-­‐related retinal bleeding, with very effective results. For a lay summary of this research, go to http://pxe.org/avastin-­‐ lucentis-­‐CATT-­‐two-­‐year-­‐results
  3. There is additional evidence that PXE is a metabolic disorder through research examining three cases of young women who acquired PXE after liver transplants4. This research gives more credibility to the hypothesis that the compound (i.e., substrate) missing in the blood of those with PXE is found in the liver. Research is currently being conducted to identify the substrate of PXE. For a lay summary of this research, go to http://pxe.org/acquired-­‐pxe-­‐after-­‐liver-­‐transplant
  4. The first study examining stem cell transplants in cases of PXE was conducted in 2012. While more research is certainly needed, transferring healthy stem cells into the liver of affected individuals may show some promise in the treatment of PXE signs and symptoms5.

Basic research discoveries are important, but we are searching for interventions that will slow down or stop PXE. We will not be satisfied until we have realized this goal. This is the yardstick by which we measure our success. Therefore, we do not count this year as a successful year in PXE research. Too many things are still undiscovered. We are still seeking the substrate (the substance that the ABCC6 protein transports), we have no treatment that will slow the progression of the disease, and we are not even able to measure the progression well, were we to find a potential treatment. The greatest advances in quality of life and true treatment for PXE continue to come from research and drug development on age-­‐related macular degeneration. In this regard, 2012 saw the introduction of new drugs and the continued success of anti-­‐angiogenesis treatments. Very few individuals’ eye disease advanced to severe vision loss compared to hundreds of individuals in prior years.

 

2012 PXE Research MeetingImg4

Because the vision, health, and the very lives of our members are at stake, we accelerate research by facilitating collaboration and cooperation in the research community. The 2012 PXE Research Meeting was an important event. Scientists from Belgium, France, Germany, Hungary, Italy, Spain, and the United States participated. US participation included representations from major research universities and the National Institutes of Health. This meeting allowed scientists to share unpublished results, strengthen collaborations and define strategies.

Researchers shared information about magnesium intake in mice as a means to mitigate the progression of PXE and showed some promising results. A magnesium clinical trial, described below, for which PXE International will recruit, commences in 2013. Discussion of the potential of additional genes involved in PXE raised questions about whether PXE is actually a spectrum of disorders. Information about potential differences in the progression of PXE in men and women could be helpful in discovering trial treatments.

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Jouni Uitto, MD, PhD Jefferson Medical College

Major outcomes of the meeting included the continued elucidation of PXE as a complex multi-­‐system disorder at the genome/environment interface. The severity of the phenotype, the age at onset, and the rate of progression are modulated by a number of factors: genetic, epigenetic and environmental, such as diet and lifestyle variables. It appears that essentially all clinical manifestations in the skin, eyes, and the cardiovascular system are caused by mineral deposits in the tissues, and prevention of these mineralization processes by approaches, such as dietary supplementation with magnesium, would be expected to be helpful in the treatment of these patients. Meanwhile, further research, including identification of molecules transported by ABCC6, is necessary for development of treatments. Validated biomarkers are needed to test emerging treatments6.

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2012 PXE International Research Meeting

 

 

Clinical Trial of Magnesium Supplementation as a Treatment for PXE

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Mark Lebwohl, MD

PXE research reached a very significant milestone in 2012 with the approval, funding and planning for the first clinical trial. This trial, conducted by Mark Lebwohl, MD at Mt. Sinai School of Medicine, is the first of its kind in PXE history. Commencing in 2013, it will test magnesium supplementation in a carefully controlled trial against a placebo, and measure the progression of PXE in people in both arms of the trial. Sharon Terry, CEO of PXE International, is a co-­‐principal investigator and is leading the effort to recruit, preliminarily screen, and support participants through education and information in the clinical trial process.

 

 

Other Research Collaborations

In a trip to China organized by Qiujie Jiang, MD, PhD, of Jefferson Medical College, Jouni Uitto, MD, PhD, Sharon and Patrick Terry all received honorary professorships from Hebei United University in Tangshan, and Dr. Uitto received a visiting professorship from the Fourth Military Medical University in Xi’an. We look forward to future research projects with these researchers in China. We will be working with them to set up a Chinese version of the PXE International website.

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Patrick Terry, President, PXE International, with Professor Lize Xiong, Dean, Fourth Military Medical University, Xi’an, China

 

Of Special Note

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Abbie Moore, PhD

Abbie Moore, PhD, joined the PXE International team mid way through this year, and brings excellent research experience in working with individuals, research methods and statistics. PXE International is fortunate in that Dr. Moore is also the Genetic Alliance Registry and BioBank Manager, and as such is expert at managing the PXE International Registry and BioBank (PIRB). The PIRB continues to be the backbone of PXE International’s research enterprise. Dr. Moore is coordinating all of PXE International’s research projects, particularly managing data and samples. She is from Texas and is enjoying the nation’s capital.

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PXE Education

One of PXE International’s top priorities is to ensure those affected with pseudoxanthoma elasticum have the highest quality educational resources to ensure they make informed decisions about their health and treatments, and can educate their doctors as well.

 

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Focus on Health

2012 was a year to focus on PXE patient health from the preventive side. As with any disease, those who are affected who maintain a healthy weight and body fat percentage, who do not smoke, and who exercise regularly may live longer and express disease symptoms to a lesser degree. In January 2012 PXE International began a year-­long, video-­‐based, monthly Health Challenge open to all PXE International membership to encourage the practice of a healthy lifestyle. A short video clip detailed each new challenge while social media energized the event. Challenge topics included: establishing walking and workout routines, eating well and in particular avoiding sugar, discovering your motivation for a healthy lifestyle, getting outside, participating in a community fitness event, venturing outside your exercise comfort zone, and mentoring a friend or family member in healthy living habits. Two eNewsletter articles from Health Challenge participants brought the fun and the work close to home. Participants recorded their monthly success or failure via online tracking, and discussed their experiences on a Facebook event page. At year’s end, it was decided that it was a tie, and two individuals were awarded the prize of $1000 each (donated by Elizabeth Terry, former Executive Director).

 

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Congratulations to Kim Griffiths and Karolina Perino

Winners of the Health Challenge

 

 

Vascular Manifestations of PXE

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In addition to the 25 medical bulletins already available explaining the signs and symptoms of PXE, in 2012 PXE International published a brand new medical bulletin describing vascular disease and its most common manifestation in PXE, peripheral arterial disease (PAD). The most common symptom of PAD is leg pain when walking, called intermittent claudication. Reinforcing 2012’s focus on health, the bulletin stresses how important it is to adopt a heart-­‐ healthy lifestyle that protects your vascular health.

 

eNewsletter - What's New?

The monthly PXE International eNewsletter, emailed to more than 2125 individuals subscribed to our listserv, is a key media for disseminating information about PXE research and events, as well as personal stories of living with PXE. 2012 saw a 60% increase in the number of issues PXE International 2012 Annual Report 8 published. Most articles drive traffic to our website, pxe.org, where readers enjoy a longer treatment of the subject and can explore this treasure trove of information. The eNewsletter was an effective tool for recruitment in the 2011-­‐2012 epidemiological study as well as in the clinical trial of magnesium supplementation in the treatment of PXE commencing 2013.

 

Lay Summaries -­‐ PXE Research Explained

In 2012, PXE International published three lay summaries of important pseudoxanthoma elasticum and related research: acquired PXE after liver transplant, two-­‐year results of an Avastin and Lucentis clinical trial, and restricting dietary magnesium in the PXE mouse. The lay summary is an important educational resource to describe the technical aspects of research in language and concepts that are accessible to the layperson.

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Webinars – Connect with PXE Experts

PXE International webinars give members from all over the world, including those who cannot travel to a meeting, an opportunity to virtually attend important presentations given by subject matter experts. They can ask questions and follow up personally with the speaker or staff. Presenters are often PXE researchers conducting critical PXE research. In 2012, five new webinars were added to the collection. Topics covered included: the search for the ABCC6 substrate, how diet affects PXE, the path from gene discovery to therapy, PXE in children, and a PXE International 2012 Annual Report 9 comprehensive PXE research update. Individuals from 63 countries downloaded webinars from the collection of 21 videos 4,200 times in 2012.

 

The Power of Social Media

PXE International’s Facebook membership and Twitter followers have grown remarkably. In 2012, our Facebook membership increased by 34% and the number of our Twitter followers rose by 45%. PXE International actively uses these familiar social networking sites to publicize our educational resources, solicit participation in research, and encourage registering with the organization and for webinars, regional meetings and the biennial conference. This year, we also created a Facebook event to manage the year-­‐long PXE Health Challenge. The majority of member posts to Facebook involve their experiences with PXE making it an excellent tool for community support. Knowledgeable staff monitors these discussions and provides timely, accurate information to group members. Also in 2012, the PXE International Facebook Group provided a platform for PXEers from the United Kingdom to connect with one of their Members of Parliament to help raise awareness of PXE in their medical community and in their government health plan administration.

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Biennial Conference – Connect and Learn

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Joe Maas, PXE International Board

PXE International hosted the 2012 Biennial Conference on September 22–23, 2012 at the Bethesda North Marriott in Bethesda, MD. The meeting served 90 affected individuals and their families from South Africa, Sweden, United Arab Emirates, Canada and the US. Top clinicians, researchers and subject matter experts presented workshops on critical topics – vascular manifestations of PXE, insurance issues, genetics and genetic testing, PXE research, PXE and the eye, women’s issues, as well as coping with and owning your PXE. Attendees benefitted from free, private vascular, low vision, and health consults conducted throughout the weekend. New offerings for the 2012 conference focused on Health and Wellness. In support of research to identify the ABCC6 substrate, a critical next step in PXE research, PXE International staff, collaborating with PXE researcher Jouni Uitto of Jefferson Medical College, held a blood collection during the conference. Samples from 74 affected and unaffected individuals were collected and are currently being analyzed by Dr. Uitto and his team. We celebrated a number of wonderful individuals who have served the community over many years. Special celebration of the contributions of Wendy Wood Hubbard and Mary LeBlanc crowned the evening.

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Passing the Torch

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Elizabeth Terry Executive Director 2010 – 2012

Elizabeth Terry, daughter of PXE International founders Pat and Sharon Terry, in 2010 committed to lead PXE International for a two-­‐year period as a way to give back to the community in which she grew up. At that time, Elizabeth, recently graduated from college, knew she had to put together a credible package, complete with milestones, to present to the board of directors – both so she would be taken seriously as well as to make the mark she had in mind. The board approved her for the proposed two-­‐year stint as Executive Director. Her two years (actually 2.5) came to an end in 2012.

Elizabeth exceeded all of her milestones, which means PXE International has risen to a new level as an organization. During her tenure, she rebranded the organization, instituted a monthly health challenge, set a rigorous fundraising challenge of $1,500,000 over five years, reinvigorated the regional meetings, infused social media tools into the communications of the organization, and renewed the website. She also provided consistent and solid coordination for the staff. In short, she was a wonderful gift to the PXE community. She was successful in the rigorous application process and has been awarded a position in the Teach for America Corps.

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Terry Mac Dermaid Executive Director

Having raised the bar for leadership considerably, it is important for PXE International to continue all of the practices Elizabeth put in place and more. Therefore, we were delighted to welcome Terry Mac Dermaid as the new Executive Director of PXE International! Prior to this, Terry worked with PXE International for more than four years as the Assistant Director. She brings a great deal of energy to everything she does. She is very organized, yet flexible. Terry has a special compassion for individuals who need our help, and a professionalism that serves our clinicians and scientists well.

Further, despite the typical challenging financial situation of a nonprofit, she is able to do a great deal with very little. Our members feel well served by Terry, and we are delighted to have her step into this senior leadership role. 

 

2013 Goals

Fund research that will accelerate the path to a therapy

  • Search for substrate
  • Clarify biomarkers
  • Design natural history clinical trial

Educate more PXEers, their families and clinicians

  • Redesign the website for greater impact and ease of use, particularly for low vision users
  • Double the publication of lay summaries of PXE research
  • Reach more members through regional meetings around the world

Improve the health and quality of life for PXEers by setting new Health Challenge goals

 

Your Role

Img25We could not do this important work without you. You are the heart and soul of our innovative efforts. We will invest in only the best science and research possible around the world. In 2012, we concluded the second year of a five-­‐year effort to raise $1.5 million for PXE research – the 15th Anniversary Challenge. Due to your generosity we are almost half way to our goal!

Let’s finish this campaign early and get to funding phenomenal research – we only need your pledges, not your money yet! We’ll bill you at your convenience! To donate please visit http://www.pxe.org/donate or email Mary Peckiconis (mpeck@pxe.org) or call 202.362.9599, extension 208.

 

 

PXE International Board of Directors

Patrick F. Terry, President

Lionel G. Bercovitch, Scientific and Medical Director

Joe Maas, Treasurer

Claire Driscoll

Jessica Harper

Kathy Hersey

Karine Unger

Judy Williams

 

Staff

Sharon F. Terry, CEO

Terry Mac Dermaid, Executive Director

Christine Vocke, Director of Education & Support

Abbie Moore, Research Coordinator

Mary Peckiconis, Bookkeeper & Office Manager

Elizabeth Terry, Director of Media & Design

Mary LeBlanc, Listserv Manager

Anna-­‐Susan Marais, South Africa Coordinator

Ian Terry, Webmaster

Erin Oliphant, Social Media Director

Rachel Koren, Research Intern

 

 

 

 

Notes

1 Jiang Q, Uitto J. Restricting dietary magnesium accelerates ectopic connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6(-­‐/-­‐)). Experimental Dermatology. 2012 Sept; 21(9):696-­‐9.

2 Kupetsky-­‐Rincon EA, Li Q, Uitto J. Magnesium reduces carotid intima-­‐media thickness in a mouse model of pseudoxanthoma elasticum: A novel treatment biomarker. Clinical and Translational Science. 2012 Jun;5(3):259-­‐64.  

3 Comparison of Age-­‐related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for treatment of neovascular age-­‐related macular degeneration: Two year results. Ophthalmology. 2012 Jul;119(7):1388-­‐98

4 Bercovitch L, Martin L, Chassaing N, et al. Acquired pseudoxanthoma elasticum presenting after liver transplantation. Journal of the American Academy of Dermatology. 2011 May;64(5):873-­‐8.

5 Jiang Q, Takahagi S, Uitto J. Administration of bone marrow derived mesenchymal stem cells into the liver: Potential to rescue pseudoxanthoma elasticum in a mouse model (abcc6(-­‐/-­‐)) [published online ahead of print Nov 26 2012]. Journal of Biomedicine and Biotechnology. 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519347/

6 Uitto J, Váradi A, Bercovitch L, Terry PF, Terry SF. Pseudoxanthoma elasticum: Progress in research towards treatment – Summary of the 2012 PXE International research meeting. Journal of Investigative Dermatology [In Press]

2006 State of the Foundation Report

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State of the Foundation Report

January 1, 2006

 

Introduction

Patrick and Sharon Terry founded PXE International in 1995 to accelerate research that will result in the treatment of pseudoxanthoma elasticum. PXE International initiates, funds, and conducts research; provides support to affected families; and supports physicians.

 

Initial Plan

Pat was a designer and engineer and Sharon was a former college chaplain when they learned in 1994 that their children (Elizabeth, born 12/12/87, and Ian, born 7/12/89) had PXE. Although they had no formal scientific background, they read medical literature, met with scientists and crafted a comprehensive research plan (Figure 1).

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Figure 1

 

The principles of the design are:

  • Fast track all phases of research simultaneously in order to avoid bottlenecks
  • Position the foundation as a firewall between patients and researchers to ensure maximum research participation
  • Initiate, fund, conduct and coordinate research in a central role to maximize efficiency and speed
  • Participate in the national genetics arena to leverage resources otherwise unavailable

 

Groundwork

The Terrys established PXE International as a 501 (c) (3) with the help of Lionel Bercovitch, MD, of Brown University.  Dr. Bercovitch is trained in both dermatology and ophthalmology and is selflessly dedicated to long hours of volunteer work for the foundation.  A dedicated board and staff provide expertise and assistance.

 

During the first few years, PXE International:

  • Assessed the state of PXE research. This included a gap analysis and the funding of small projects in the gap as a way to gather enough data to apply for government and industry grants.
  • Planned a cohesive strategy to avoid overlap and encourage innovative collaborative methods.
  • Established a large registry (Figure 2) to form the cohort needed for robust studies.
  • Founded the PXE International Blood and Tissue Bank, whose samples now number in the thousands. This lay-managed and -owned bank was the first of its kind and is the model on which the Genetic Alliance BioBank is founded.

All activities are funded through private donations.

 

Discovery of the Gene Associated with PXE

The PXE International Blood and Tissue Bank accelerated the discovery of the PXE gene, and the research was enhanced by the participation of Patrick and Sharon Terry. As result of their material involvement in the discovery, PXE International is a co-owner of the patent on the PXE gene.   The patent issued in August 2004.  It has been licensed to Transgenomic for development of a diagnostic test – see below.

 

Sharon Terry is a co-author on two back-to-back papers in Nature Genetics describing the PXE gene. This is unique for two reasons. When papers are published back-to-back, it is rare that one author collaborates with both groups. PXE International works extensively with both of the labs that published in that issue and helped to coordinate the simultaneous publication. It is also exceedingly rare for a non-Ph.D./M.D. to publish a paper in a journal of such high impact. (Ms. Terry has an M.A. in Religious Studies.)

 

Epidemiological Study

Seeding various projects paid off for PXE International; they first began to be awarded grant money in September 1998. The Simmons Foundation awarded PXE International a grant of $20,000 for an epidemiological study of the manifestations and progression of PXE in a large number of individuals. Over 600 questionnaires were completed. The Center for Disease Control in Atlanta, GA, donated time to help analyze the data.

 

Although there are a large number of case studies on PXE, it is necessary to analyze data on a large group of individuals in order to understand the wide spectrum of the condition. In fact, case reports tend to focus on individuals with the most severe signs and symptoms, leading clinicians and patients to think the disease is worse than it is. Analysis of the data is almost complete and plans for correlating the data to genetic information about individuals are under way.

 

In the process of analyzing the data from over 600 surveys, PXE International was able to study and publish papers in peer-reviewed journals.  These include a study on PXE and Pregnancy (Attach), Mammography and PXE (Attach), Testicular Microlithiasis and PXE (Attach).  We are in the process of analyzing the pediatric data to describe the natural history of PXE in children.

 

Other genetics groups recognize PXE International for its profoundly innovative approach to research of rare diseases. PXE International is lauded internationally for creating a new paradigm for lay advocacy groups initiating and conducting research -Articles have appeared in major newspapers and magazines describing the novelty and progression of the model.

 

Mutation Analysis

PXE International piloted a system to combine the standardization of mutation detection and the input of phenotypic information. PXE International placed three dHPLC machines in labs in Philadelphia, Ghent (Belgium) and Johannesburg (South Africa). State-of-the-art informatics were used to analyze the data.   Over 100 mutations were discovered as a result of this work.  In addition, it forms the basis of the development of a diagnostic kit for pseudoxanthoma elasticum.

 

Using advanced statistical software, we determined that correlations between mutations with clinical phenotype do not exist.  Several sub-studies evolved from the mutation analysis, including one in multiple generation families, and one a rare phenotype of PXE with eye but no skin manifestations.

 

Diagnostic Kit

PXE International is bringing a diagnostic test to the FDA for approval.  This will be the first diagnostic test for a rare disease to be presented to the FDA.  Our intention is to make the test affordable, of the highest quality, with broad access and appropriate genetic counseling.  This test will not only help families understand if siblings of affected individuals have PXE, but may also allow therapies to be targeted to specific mutations determine by the test.

 

Cellular and Molecular Studies

PXE International is funding research in a number of labs studying cell structure and function. One such study includes cytochemical and immunocytochemical localizations, X-ray microanalysis, and confocal microscopy image analysis. This effort will be instrumental in characterizing subcellular organelle behaviors, cellular behavior, and tissue-specific phenotypes.

 

Another laboratory is conducting cellular protein assay experiments for functional understanding of recombinant protein using the baculovirus insect cell system. This research seeks to characterize the previously observed protein degradation, cellular response to accumulation of unfolded mutant integral membrane proteins in the endoplasmic reticulum, posttranslational modification, and purification of recombinant ABCC6/MRP6 proteins in cells using recombinant baculovirus transfer cell expression plasmids. The purpose of this work is protein purification, targeted peptide design, peptide purification, testing of customized monoclonal antibodies, protein expression characterization, enzymatic functional description, structural dynamic range, and primary functional analysis of wild type and mutant proteins.

 

PXE Research Meeting

A major accomplishment this year was producing a comprehensive summary of the PXE 2004 Research Meeting (available upon request). The meeting was held October 13 and 14, 2004 at the Pooks Hill Marriott, Bethesda, MD, a handicapped accessible hotel.  The meeting was coordinated and co-sponsored by PXE International.  This symposium capitalized on significant progress made in basic understanding of the genetics of PXE and the structural components affected by PXE since the last research meeting in 1997. The overall goal of the Symposium was to provide a forum for investigators to discuss relevant advances in transporter biology, metabolism, genetics, and epidemiology and for clinically oriented colleagues and PXE International to jointly plan for future research and translational applications.  The audience represented a broad spectrum of individuals with varying expertise including practicing clinicians caring for patients with PXE, physician-scientists and basic science investigators and lay leaders, all of whom share an interest in PXE.

The specific aim of this Symposium was to provide a forum for a cross-fertilization of ideas between the basic and clinical sciences that was not achievable in more general meetings, and that is essential to translational research. 

 

The development of a formal research consortium was a major result of this meeting.  This will allow us to proceed with a clinical study.  The major issues that resulted are:

Genotype/Phenotype

Geno/pheno correlations

Variability in penetrance, expressivity and progression

From mutations to phenotypes

Identical genotypes –

Genotype people without mutations in the coding region

 

Genetics

Is there another locus?  SNPs

Modifier genes- find that locus

Gene chips?

Another locus, noncoding region

Is the deletion a problem?

 

Gene & Protein Function

Function of MRP6

Look at MRP expression over lifespan

Post translational modification

Normal function

Consequences of mutations – allelic therapeutic approach

Validated assay – small molecule screening- both molecules that block and those that perform, whole family screening

Synonymous alterations – codon usage – alternative splicing

Antibodies expression – in the ones you cannot find mutations

Inside out vesicles – purify and put them in

Make chimeric protein – Jouni didn’t find anything

GFP reporter

Inhibitors – hepatosycle +/- inhibitors

Basic Bruch’s membrane – research angiogenesis, roll of ABCC6 in eye – choroidal fibroblasts?

 

Environmental factors

 

Diagnostic

Understand diagnostic criteria – what we will we accept as biomarker

Place for DNA diagnostics – to determine potential treatment protocols

Need to narrow the clinical diagnosis

Definitive statement – recessive inheritance

Diagnostic criteria

Females to males – genotype sibs and families

 

Models

Characterize mouse model for mechanisms of mineralization

Liver expression – mouse liver transplant

Regulation of MRP6 – at protein level – like MRP2 – targeting and cycling – Put PDZ on MRP6 Would it appear in bile of mouse – do mass spec – at transcriptional level

Evolutionary and embryonic models – c. elegans

Find models – smaller and larger

Zebra fish – when does gene turn on why – is it in the eye/

 

Pathobiology

Assay for pump function

What about overexpression – cytotoxic drugs and the mouse redox system

Can we distinguish between PXE and normal cells?

What compounds might make the PXE cell look like a normal cell?

Pathomechanisms

Pathobiology

 

Clinical Study

NIH clinical study – develop protocol

 

Treatments

Treatments, model systems?

Issues of antioxidants reversing damage?

Treatments of cells with small molecules

Use RNAi

 

Research Structure

Consortium – clinical and molecular

 

Clinical Study at NIH

 

With support from the NIH, PXE International is about to launch a 3-year clinical investigation into the manifestations of PXE.  This study will focus on characterizing the clinical manifestations of PXE – something that is not often done well in rare diseases, which usually are characterized by case reports of the extremes of the phenotype.  After the initial characterization, we will be looking at a variety of possible treatments and interventions, with the goal of establishing a clinical trial in the three-year project.

 

Conclusion

Except for projects supported by grants from the Simmons Foundation, NIH and Transgenomic, all PXE International research is funded through private donations. The seeds planted by these small donations have grown into grants from foundations, companies and the government.

 

PXE International is in a unique and powerful position to advocate for individuals affected by PXE, and our work is vital to them and to others facing similar struggles. It is the only hope for many individuals who desperately fear blindness. PXE International is also a role model for many other groups throughout the world .

 

Despite the now millions of dollars we have placed into service on PXE research via the NIH, much remains to be done.  In the United States, the NIH funds basic research.  While this research is critical, we need to move to the next step and look at translating research into treatments.  We have a number of labs ready to work on this – it is only up to us to garner the funds to move forward. It is essential, not only to those affected by PXE but also to other groups, to analyze the incredible gold mine of data we have gathered in our search to understand and meet the challenge of PXE. Working into the wee hours of the morning, our fatigue abates through a burning desire to prevent blindness and other difficulties for the thousands of people on our registry. And in so doing, to create a new model of partnership between practitioners and researchers and the individuals they serve.

 

2005 State of the Foundation Report

State of the Foundation Report Logo

January 1, 2005

 

Introduction

Patrick and Sharon Terry founded PXE International in 1995 to accelerate research that will result in the treatment of pseudoxanthoma elasticum.  PXE International initiates, funds, and conducts research; provides support to affected families; and supports physicians.

 

Initial Plan

Pat was a designer and engineer and Sharon was a former college chaplain when they learned in 1994 that their children (Elizabeth, born 12/12/87, and Ian, born 7/12/89) had PXE. Although they had no formal scientific background, they read medical literature, met with scientists, and crafted a comprehensive research plan (Figure 1).

 

Fig1
PXE Research Plan

 

The principles of the design are:

  • Fast track all phases of research simultaneously in order to avoid bottlenecks
  • Position the foundation as a firewall between patients and researchers to ensure maximum research participation
  • Initiate, fund, conduct and coordinate research in a central role to maximize efficiency and speed
  • Participate in the national genetics arena to leverage resources otherwise unavailable

 

Groundwork

The Terrys established PXE International as a 501 (c) (3) with the help of Lionel Bercovitch, MD, of Brown University.  Dr. Bercovitch is trained in both dermatology and ophthalmology and is selflessly dedicated to long hours of volunteer work for the foundation.  A dedicated board and staff provide expertise and assistance.

 

During the first few years, PXE International:

  • Assessed the state of PXE research. This included a gap analysis and the funding of small projects in the gap as a way to gather enough data to apply for government and industry grants.
  • Planned a cohesive strategy to avoid overlap and encourage innovative collaborative methods.
  • Established a large registry (Figure 2) to form the cohort needed for robust studies.
  • Founded the PXE International Blood and Tissue Bank, whose samples now number in the thousands. This lay-managed and -owned bank was the first of its kind and is the model on which the Genetic Alliance BioBank is founded.
Fig2
Growth in Number of Affected Individuals Registered

 

Discovery of the Gene Associated with PXE

The PXE International Blood and Tissue Bank accelerated the discovery of the PXE gene, and the research was enhanced by the participation of Patrick and Sharon Terry.  As a result of their material involvement in the discovery, PXE International is a co-owner of the patent on the PXE gene.  The patent issued in August 2004.  It has been licensed to Transgenomic for development of a diagnostic test.  Refer to the section titled Diagnostic Kit.

Sharon Terry is a co-author on two back-to-back papers in Nature Genetics describing the PXE gene.  This is unique for two reasons.  When papers are published back-to-back, it is rare that one author collaborates with both groups.  PXE International works extensively with both of the labs that published in that issue and helped to coordinate the simultaneous publication.  It is also exceedingly rare for a non-Ph.D./M.D. to publish a paper in a journal of such high impact.  (Ms. Terry has an M.A. in Religious Studies.)

 

Epidemiological Study

Seeding various projects paid off for PXE International; they first began to be awarded grant money in September 1998.  The Simmons Foundation awarded PXE International a grant of $20,000 for an epidemiological study of the manifestations and progression of PXE in a large number of individuals.  Over 600 questionnaires were completed.  The Center for Disease Control in Atlanta, GA, donated time to help analyze the data.

Although there are a large number of case studies on PXE, it is necessary to analyze data on a large group of individuals in order to understand the wide spectrum of the condition.  In fact, case reports tend to focus on individuals with the most severe signs and symptoms, leading clinicians and patients to think the disease is worse than it is.  Analysis of the data is almost complete and plans for correlating the data to genetic information about individuals are under way.

In the process of analyzing the data from over 600 surveys, PXE International was able to study and publish papers in peer-reviewed journals.  These include a study on PXE and pregnancy[1], mammography and PXE[2], and testicular microlithiasis and PXE[3].  At this time, pediatric data is being analyzed to describe the natural history of PXE in children.

Other genetics groups recognize PXE International for its profoundly innovative approach to research of rare diseases.  PXE International is lauded internationally for creating a new paradigm for lay advocacy groups initiating and conducting research.  Articles have appeared in major newspapers and magazines describing the novelty and progression of the model.

 

Mutation Analysis

PXE International piloted a system to combine the standardization of mutation detection and the input of phenotypic information.  PXE International placed three dHPLC machines in labs in Philadelphia, Ghent (Belgium) and Johannesburg (South Africa).  State-of-the-art informatics was used to analyze the data.  Over 100 mutations were discovered as a result of this work.  In addition, it forms the basis of the development of a diagnostic kit for pseudoxanthoma elasticum.

Using advanced statistical software, it was determined that correlations between mutations with clinical phenotype do not exist.  Several sub-studies evolved from the mutation analysis, including one in multiple generation families, and one a rare phenotype of PXE with eye but no skin manifestations.

 

Diagnostic Kit

PXE International is bringing a diagnostic test to the FDA for approval.  This will be the first diagnostic test for a rare disease to be presented to the FDA. The intention is to make the test affordable, of the highest quality, with broad access and appropriate genetic counseling.  This test will not only help families understand if siblings of affected individuals have PXE, but may also allow therapies to be targeted to specific mutations determine by the test.

 

Cellular and Molecular Studies

PXE International is funding research in a number of labs studying cell structure and function.  One such study includes cytochemical and immunocytochemical localizations, X-ray microanalysis, and confocal microscopy image analysis.  This effort will be instrumental in characterizing subcellular organelle behaviors, cellular behavior, and tissue-specific phenotypes.

Another laboratory is conducting cellular protein assay experiments for functional understanding of recombinant protein using the baculovirus insect cell system.  This research seeks to characterize the previously observed protein degradation, cellular response to accumulation of unfolded mutant integral membrane proteins in the endoplasmic reticulum, posttranslational modification, and purification of recombinant ABCC6/MRP6 proteins in cells using recombinant baculovirus transfer cell expression plasmids.  The purpose of this work is protein purification, targeted peptide design, peptide purification, testing of customized monoclonal antibodies, protein expression characterization, enzymatic functional description, structural dynamic range, and primary functional analysis of wild type and mutant proteins.

 

PXE Research Meeting

A major accomplishment this year was the PXE 2004 Research Meeting.  PXE International was awarded an R13 grant for partial support for a Symposium entitled "PXE Research 2004".  The meeting was held October 13 and 14, 2004 at the Pooks Hill Marriott, Bethesda, MD, a handicapped accessible hotel.  The meeting was coordinated and co-sponsored by PXE International. 

The Symposium capitalized on significant progress made in basic understanding of the genetics of PXE and the structural components affected by PXE since the last research meeting in 1997.  Though these advances were significant, they highlighted a lack of linkage between the basic genetic and molecular advances and the pathogenesis of this disease.  This meeting reviewed progress in genetics, cellular and molecular biology, catalyzed the current research through knowledge and tools of related research, provided the foundation with a comprehensive research plan and determined best practices for clinical care of individuals affected by PXE. 

The overall goal of the Symposium was to provide a forum for investigators to discuss relevant advances in transporter biology, metabolism, genetics, and epidemiology and for clinically oriented colleagues and PXE International to jointly plan for future research and translational applications.  The audience represented a broad spectrum of individuals with varying expertise including practicing clinicians caring for patients with PXE, physician-scientists and basic science investigators and lay leaders, all of whom share an interest in PXE.

The specific aim of the Symposium was to provide a forum for a cross-fertilization of ideas between the basic and clinical sciences that was not achievable in more general meetings, and that is essential to translational research.  The presence of clinical investigators from the disciplines of dermatology, ophthalmology, gastroenterology and cardiology allowed broad-based discussion of PXE with its many systemic effects, to inform the basic science to focus it, and conversely to set best practice standards for data collection and clinical care.  Special attention was paid to the involvement of women, young investigators and trainees in this meeting, and involving both scientists and clinicians from underrepresented communities.

The development of a formal research consortium was a major result of this meeting.  This will allow us to proceed with a clinical study.

 

Clinical Study at NIH

With support from the NIH, PXE International is about to launch a three-year clinical investigation into the manifestations of PXE.  This study will focus on characterizing the clinical manifestations of PXE – something that is not often done well in rare diseases, which usually are characterized by case reports of the extremes of the phenotype.  After the initial characterization, a variety of possible treatments and interventions will be examined with the goal of establishing a clinical trial in the three-year project.

 

PXE International in the Genetics Community

Sharon and/or Patrick Terry serve on these committees, which give the foundation a central position in the genetics community:

  • President & CEO, Genetic Alliance
  • Founder, Personalized Medicine Coalition Board of Directors
  • Founding President, International Genetic Alliance (IGA)
  • Founder, Genomic Health, Inc.
  • Liaison, National Advisory Council for Human Genome Research
  • Member, Colorectal Cancer Coalition Advisory Board
  • Member, Cellular, Tissue, and Gene Therapies Advisory Committee, FDA (formerly Center for Biologics Evaluation and Research Advisory Committee, FDA)
  • Member, Center on Information and Study on Clinical Research Participation (CISCRP) Board of Directors
  • Member, DNA Direct Board of Directors
  • Office of Rare Diseases, NIH and CDC, Rare Disease Testing Working Group
  • Member, Genetics Services Research Advisory Board
  • President, Genetic Alliance Biobank Board of Directors
  • Member, National Institute of Arthritis Musculoskeletal and Skin Diseases Council
  • Member, Biotechnology Institute Board of Directors
  • Member, American Society of Matrix Biology Council
  • Member, Advisory Board, Genetics and Public Policy Center, Johns Hopkins University
  • Member, Scientific Council, PXE France
  • Member, Professional Advisory Board, Autosomal Recessive Polycystic Kidney Disease Alliance
  • Appointed Member, The American Society of Human Genetics Information and Education Commitee
  • Member, Professional Advisory Board, Aneurysm Outreach Inc.
  • Ad Hoc Committee of Experts on IRBs and Informed Consent, HHS Secretary's Advisory Council on Genetic Testing
  • Member, Advisory Committee on Informed Consent, Centers for Disease Control, Atlanta, Georgia
  • Appointed Member, Ethical, Legal and Social Issues Research Advisors, NIH
  • President, Coalition of Heritable Disorders of Connective Tissue
  • Representative to the Research Council, American Academy of Dermatology
  • Consumer representative, Women’s Dermatology Committee, American Academy of Dermatology
  • Member, Ad-hoc Committee for Consumer Issues, The American Society of Human Genetics
  • Founder, Co-chair, Coalition of Advocates for Research on the Eye (CARE)

 

Conclusion

Except for projects supported by grants from the Simmons Foundation, NIH and Transgenomic, all PXE International research is funded through private donations.  The seeds planted by these small donations have grown into grants from foundations, companies and the government.

PXE International is in a unique and powerful position to advocate for individuals affected by PXE, and our work is vital to them and to others facing similar struggles.  It is the only hope for many individuals who desperately fear blindness.  PXE International is also a role model for many other advocacy groups throughout the world.

Despite the now millions of dollars we have placed into service on PXE research via the NIH, much remains to be done.  In the United States, the NIH funds basic research.  While this research is critical, PXE International needs to move to the next step and look at translating research into treatments.  There are a number of labs ready to work on this – it is up to us to garner the funds to move forward.  It is essential, not only to those affected by PXE but also to other groups, to analyze the incredible gold mine of data gathered in the search to understand and meet the challenge of PXE.  Working into the wee hours of the morning, fatigue abates through a burning desire to prevent blindness and other difficulties for the thousands of people on the PXE International registry, and in so doing, to create a new model of partnership between practitioners and researchers and the individuals they serve.

 

[1] Bercovitch L, Leroux T, Terry S, Weinstock MA.Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum. British Journal of Dermatology. 2004;151:1011-1018.

[2] Bercovitch L, Schepps B, Koelliker S, Magro C, Terry S, Lebwohl M. Mammographic findings in pseudoxanthoma elasticum. Journal of the American Academy of Dermatology.2003;48:359-66.

[3] Bercovitch RS, Januario JJ, Terry SF, Boekeheide K, Podis AD, Dupuy DE, Bercovitch LG. Testicular microlithiasis in pseudoxanthoma elasticum. Radiology. In press, 2005.

2007 State of the Foundation Report

State of the Foundation Report Logo

 

September 30, 2007

End of Fiscal Year 2007

 

 

Introduction

Patrick and Sharon Terry founded PXE International in 1995 to accelerate research that will result in the treatment of pseudoxanthoma elasticum.  PXE International initiates, funds, and conducts research; provides support to affected families; and supports physicians.

 

Initial Plan

Pat was a designer and engineer and Sharon was a former college chaplain when they learned in 1994 that their children (Elizabeth, born 12/12/87, and Ian, born 7/12/89) had PXE. Although they had no formal scientific background, they read medical literature, met with scientists and crafted a comprehensive research plan (Figure 1).

 

Fig1
Figure 1 - PXE Research Plan

 

The principles of the design are:

  • Fast track all phases of research simultaneously in order to avoid bottlenecks
  • Position the foundation as a firewall between patients and researchers to ensure maximum research participation
  • Initiate, fund, conduct and coordinate research in a central role to maximize efficiency and speed
  • Participate in the national genetics arena to leverage resources otherwise unavailable

 

Groundwork

The Terrys established PXE International as a 501 (c) (3) with the help of Lionel Bercovitch, MD, of Brown University.  Dr. Bercovitch is trained in both dermatology and ophthalmology and is selflessly dedicated to long hours of volunteer work for the foundation.  A dedicated board and staff provide expertise and assistance.

 

During the first few years, PXE International:

  • Assessed the state of PXE research. This included a gap analysis and the funding of small projects in the gap as a way to gather enough data to apply for government and industry grants.
  • Planned a cohesive strategy to avoid overlap and encourage innovative collaborative methods.
  • Established a large registry (Figure 2) to form the cohort needed for robust studies.
  • Founded the PXE International Blood and Tissue Bank, whose samples now number in the thousands. This lay-managed and -owned bank was the first of its kind and is the model on which the Genetic Alliance BioBank is founded.

 

Fig2
Figure 2

 

Staffing

PXE International staffing grew in a meaningful way this year.  Delia Clayton was hired as the second full-time employee, as assistant director, to join Sharon Terry, who serves as Executive Director.  In addition, Emilie Lamb was hired as the second part-time research assistant, to replace Sophia Vourthis, who graduated and returned to Washington State.  Christine Vocke was promoted to Director of Education and Information.  Terry Mac Dermaid continues as webmaster, and Mary Peckiconis as bookkeeper.  Donna Foster continues to oversee the books.  Mary LeBlanc serves in a volunteer capacity as listserv manager.

 

Discovery of the Gene Associated with PXE

The PXE International Blood and Tissue Bank accelerated the discovery of the PXE gene, and the research was enhanced by the participation of Patrick and Sharon Terry.  As a result of their material involvement in the discovery, PXE International is a co-owner of the patent on the PXE gene.  The patent issued in August 2004.  It has been licensed to Transgenomic for development of a diagnostic test.  Refer to the section titled Diagnostic Kit.

Sharon Terry is a co-author on two back-to-back papers in Nature Genetics describing the PXE gene.  This is unique for two reasons.  When papers are published back-to-back, it is rare that one author collaborates with both groups.  PXE International works extensively with both of the labs that published in that issue and helped to coordinate the simultaneous publication.  It is also exceedingly rare for a non-Ph.D./M.D. to publish a paper in a journal of such high impact.  (Ms. Terry has an M.A. in Religious Studies.)

 

Epidemiological Study

Seeding various projects paid off for PXE International; they first began to be awarded grant money in September 1998.  The Simmons Foundation awarded PXE International a grant of $20,000 for an epidemiological study of the manifestations and progression of PXE in a large number of individuals.  Over 600 questionnaires were completed. The Center for Disease Control in Atlanta, GA, donated time to help analyze the data.

Although there are a large number of case studies on PXE, it is necessary to analyze data on a large group of individuals in order to understand the wide spectrum of the condition.  In fact, case reports tend to focus on individuals with the most severe signs and symptoms, leading clinicians and patients to think the disease is worse than it is.  Analysis of the data is almost complete and plans for correlating the data to genetic information about individuals are under way.

In the process of analyzing the data from over 600 surveys, PXE International was able to study and publish papers in peer-reviewed journals.  These include a study on PXE and pregnancy[1], mammography and PXE[2], and testicular microlithiasis and PXE[3].  At this time, pediatric data is being analyzed to describe the natural history of PXE in children.

Other genetics groups recognize PXE International for its profoundly innovative approach to research of rare diseases.  PXE International is lauded internationally for creating a new paradigm for lay advocacy groups initiating and conducting research.  Articles have appeared in major newspapers and magazines describing the novelty and progression of the model.

 

Mutation Analysis

PXE International piloted a system to combine the standardization of mutation detection and the input of phenotypic information.  PXE International placed three dHPLC machines in labs in Philadelphia, Ghent (Belgium) and Johannesburg (South Africa).  State-of-the-art informatics was used to analyze the data.  To date we have discovered over 270 mutations as a result of this work.  In addition, this work forms the basis of the development of a diagnostic test for pseudoxanthoma elasticum.

Using advanced statistical software, it was determined that correlations between mutations with clinical phenotype do not exist.  Several sub-studies evolved from the mutation analysis, including one in multiple generation families, and one a rare phenotype of PXE with eye but no skin manifestations.

 

Diagnostic Kit

PXE International, as part of the federal Collaboration, Education and Test Translation program, has begun to offer a genetic test for PXE.  This is first diagnostic test for PXE. We have worked, with GeneDx, to make the test affordable, high quality, with broad access and appropriate genetic counseling.  This test helps families understand if siblings of affected individuals have PXE, and may also allow therapies to be targeted to specific mutations determined by the test.

 

Cellular and Molecular Studies

PXE International is funding research in a number of labs studying cell structure and function.  One such study includes cytochemical and immunocytochemical localizations, X-ray microanalysis, and confocal microscopy image analysis.  This effort will be instrumental in characterizing subcellular organelle behaviors, cellular behavior, and tissue-specific phenotypes.

Another laboratory is conducting cellular protein assay experiments for functional understanding of recombinant protein using the baculovirus insect cell system.  This research seeks to characterize the previously observed protein degradation, cellular response to accumulation of unfolded mutant integral membrane proteins in the endoplasmic reticulum, posttranslational modification, and purification of recombinant ABCC6/MRP6 proteins in cells using recombinant baculovirus transfer cell expression plasmids.  The purpose of this work is protein purification, targeted peptide design, peptide purification, testing of customized monoclonal antibodies, protein expression characterization, enzymatic functional description, structural dynamic range, and primary functional analysis of wild type and mutant proteins.

 

PXE Research Meeting

PXE International is applying for another R13 grant for partial support for a Symposium entitled "PXE Research 2008".  The meeting will be held September 2008 at the North Bethesda Marriott in suburban DC.  The meeting will be coordinated and co-sponsored by PXE International. 

The overall goal of the meeting will be to provide a forum for investigators to discuss relevant advances in transporter biology, metabolism, genetics, and epidemiology and for clinically oriented colleagues and PXE International to jointly plan for future research and translational applications.  The audience will represent a broad spectrum of individuals with varying expertise including practicing clinicians caring for patients with PXE, physician-scientists and basic science investigators and lay leaders, all of whom share an interest in PXE.

 

Clinical Study at NIH

With support from the NIH, PXE International is about to launch a three-year clinical investigation into the manifestations of PXE.  This study will focus on characterizing the clinical manifestations of PXE – something that is not often done well in rare diseases, which usually are characterized by case reports of the extremes of the phenotype.  After the initial characterization, a variety of possible treatments and interventions will be examined with the goal of establishing a clinical trial in the three-year project.

 

PXE International in the Genetics Community

Sharon and/or Patrick Terry serve on these committees, which give the foundation a central position in the genetics community:

  • President & CEO, Genetic Alliance
  • Founding President, Genetic Alliance BioBank
  • Member, Google Health Advisory Board
  • Founder, Personalized Medicine Coalition Board of Directors
  • Founding member, 21st Century Medicine Coalition
  • Founding President, International Genetic Alliance (IGA)
  • Founder, Genomic Health, Inc.
  • Member, Institute of Medicine Translational Research Roundtable
  • President, Coalition for Genetic Fairness
  • Liaison, National Advisory Council for Human Genome Research
  • Member, Colorectal Cancer Coalition Advisory Board
  • Member, Cellular, Tissue, and Gene Therapies Advisory Committee, FDA (formerly Center for Biologics Evaluation and Research Advisory Committee, FDA)
  • Member, Center on Information and Study on Clinical Research Participation (CISCRP) Board of Directors
  • Member, DNA Direct Board of Directors
  • Office of Rare Diseases, NIH and CDC, Rare Disease Testing Working Group
  • Member, Genetics Services Research Advisory Board
  • Member, Biotechnology Institute Board of Directors
  • Member, Scientific Council, PXE France
  • Member, Professional Advisory Board, Autosomal Recessive Polycystic Kidney Disease Alliance
  • Chair, American Society of Human Genetics Social Issues Committee
  • Member, Professional Advisory Board, Aneurysm Outreach Inc.
  • Member, Advisory Committee on Informed Consent, Centers for Disease Control, Atlanta, Georgia
  • Co-President, Coalition of Heritable Disorders of Connective Tissue
  • Founder, Co-chair, Coalition of Advocates for Research on the Eye (CARE)

 

Conclusion

Except for projects supported by grants from the Simmons Foundation, NIH and Transgenomic, all PXE International research is funded through private donations.  The seeds planted by these small donations have grown into grants from foundations, companies and the government.

PXE International is in a unique and powerful position to advocate for individuals affected by PXE, and our work is vital to them and to others facing similar struggles.  It is the only hope for many individuals who desperately fear blindness.  PXE International is also a role model for many other advocacy groups throughout the world.

Despite the now millions of dollars we have placed into service on PXE research via the NIH, much remains to be done.  In the United States, the NIH funds basic research.  While this research is critical, PXE International needs to move to the next step and look at translating research into treatments.  There are a number of labs ready to work on this – it is up to us to garner the funds to move forward.  It is essential, not only to those affected by PXE but also to other groups, to analyze the incredible gold mine of data gathered in the search to understand and meet the challenge of PXE.  Working into the wee hours of the morning, fatigue abates through a burning desire to prevent blindness and other difficulties for the thousands of people on the PXE International registry, and in so doing, to create a new model of partnership between practitioners and researchers and the individuals they serve.

 

[1] Bercovitch L, Leroux T, Terry S, Weinstock MA.Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum. British Journal of Dermatology. 2004;151:1011-1018.

[2] Bercovitch L, Schepps B, Koelliker S, Magro C, Terry S, Lebwohl M. Mammographic findings in pseudoxanthoma elasticum. Journal of the American Academy of Dermatology.2003;48:359-66.

[3] Bercovitch RS, Januario JJ, Terry SF, Boekeheide K, Podis AD, Dupuy DE, Bercovitch LG. Testicular microlithiasis in pseudoxanthoma elasticum. Radiology. In press, 2005.

2002 State of the Foundation Report

State of the Foundation Report Logo

June 30, 2002

 

Introduction

Patrick and Sharon Terry founded PXE International in 1995 to create the interest and support necessary to accelerate research into the cause and treatment of pseudoxanthoma elasticum. PXE International initiates, funds, and conducts research; provides support to affected families; and supports physicians.

 

Initial Plan

Pat was a designer and engineer and Sharon was a former college chaplain when they learned in 1994 that their children (Elizabeth, born 12/12/87, and Ian, born 7/12/89) had PXE. Although they had no formal scientific background, they met with scientists who had authored scientific papers about PXE and crafted a plan (Figure 1).

 

Figure 1

 

The principles of the design are:

  • Fast track all phases of research simultaneously in order to avoid bottlenecks
  • Position the foundation as a firewall between patients and researchers to ensure maximum research participation
  • Initiate, fund, conduct and coordinate research in a central role to maximize efficiency and speed
  • Participate in the national genetics arena to leverage resources otherwise unavailable

 

Groundwork

The Terrys established PXE International with the help of Lionel Bercovitch, MD.  Dr. Bercovitch is trained in both dermatology and ophthalmology and is selflessly dedicated to long hours of volunteer work for the foundation.  A dedicated board and staff provide expertise and assistance.

 

During the first few years, PXE International:

  • Assessed the state of PXE research. This included a gap analysis and the funding of small projects in the gap as a way to gather enough data to apply for government and industry grants.
  • Planned a cohesive strategy to avoid overlap and encourage innovative collaborative methods.
  • Established a large registry (Figure 2) to form the cohort needed for robust studies.
  • Founded the PXE International Blood and Tissue Bank, whose samples now number in the thousands. This lay-managed and -owned bank was the first of its kind and is now a model for other disease groups.
  • All activities were funded through private donations.

Figure 2

Registry Growth

 

Discovery of the Gene Associated with PXE

The PXE International Blood and Tissue Bank accelerated the discovery of the PXE gene, and the research was enhanced by the participation of Patrick and Sharon Terry. As result of their material involvement in the discovery, PXE International is a co-applicant for the patent on the PXE gene.

Sharon Terry is a co-author on two back-to-back papers in Nature Genetics describing the PXE gene. This is unique for two reasons. When papers are published back-to-back, it is rare that one author collaborates with both groups. PXE International works extensively with both of the labs that published in that issue and helped to coordinate the simultaneous publication. It is also exceedingly rare for a non-Ph.D./M.D. to publish a paper in a journal of such high impact. (Ms. Terry has an M.A. in Religious Studies.)

 

Epidemiological Study

Seeding various projects paid off for PXE International; the first began to be awarded grant money in September 1998. The Simmons Foundation awarded PXE International a grant of $20,000 for an epidemiological study of the manifestations and progression of PXE in a large number of individuals. Over 600 questionnaires were completed. The Center for Disease Control in Atlanta, GA, donated time to help analyze the data.

Although there are a large number of case studies on PXE, it is necessary to analyze data on a large group of individuals in order to understand the wide spectrum of the condition. In fact, case reports tend to focus on individuals with the most severe signs and symptoms, leading clinicians and patients to think the disease is worse than it is. Analysis of the data is almost complete and plans for correlating the data to genetic information about individuals are under way.

Other genetics groups recognize PXE International for its profoundly innovative approach to research of rare diseases. PXE International is lauded internationally for creating a new paradigm for lay advocacy groups initiating and conducting research (See Attachment A ñ Kolata, A Familyís Goal is Met and a Gene is Found, New York Times, May 28, 2000; Attachment B ñ Solovich, The Citizen Scientists, Wired Magazine, September 9, 2001 [http://www.wired.com/wired/archive/9.09/disease.html] and Attachment C ñ Allen, Who Owns My Disease?, Mother Jones Magazine, November/December 2001 [http://www.motherjones.com/magazine/ND01/gene.html]).

 

Mutation Analysis

PXE International is piloting a system to combine the standardization of mutation detection and the input of phenotypic information. The search for mutations in the PXE gene continues, using the PXE International Blood and Tissue Bank. PXE International placed four dHPLC machines in labs in Philadelphia, Honolulu, Ghent (Belgium) and Johannesburg (South Africa). State-of-the-art informatics will be used to analyze the data.

Using advanced statistical software, we will correlate mutations with phenotype, and several advances will be possible. It will be possible to predict the manifestations toward which an individual with PXE might be predisposed. This would allow modifications of diet and lifestyle that might mitigate some of the effects of PXE. It will be possible to determine if an individual is a carrier of the gene and so may be predisposed to other conditions or symptoms, such as cardiovascular disease (Attachment D ñ UH Discovery May Cut Heart Disease, The Honolulu Star, June 2, 2002 [http://www.pxe.org/news/honolulu_060200.html]).

Most important, this correlation may lead to ideas about treatments and cure. If researchers determine that a specific mutation causes blindness, then knowing how to reverse the effects of that mutation will be crucial in slowing and stopping the progression of PXE.

 

Mouse Model

PXE International is funding the creation of a knockout mouse and will examine the effects of this alteration on the mouse. Although PXE in the mouse might manifest itself quite differently from PXE in humans, the researcher we have funded at Jackson Laboratory is exceptionally skilled in discovering the parallels between mouse and human phenotypes. This research will aid in the discovery of the effects of PXE on various body systems.

Since preliminary data indicates that clinical phenotypes do not correlate with genotype, this project expands the concept of phenotype to include cellular and molecular characteristics.

 

Cellular and Molecular Studies

PXE International is funding research in a number of labs studying cell structure and function. One such study includes cytochemical and immunocytochemical localizations, X-ray microanalysis, and confocal microscopy image analysis. This effort will be instrumental in characterizing subcellular organelle behaviors, cellular behavior, and tissue-specific phenotypes.

Another laboratory will conduct the cellular protein assay experiments for functional understanding of recombinant protein using the baculovirus insect cell system. This research seeks to characterize the previously observed protein degradation, cellular response to accumulation of unfolded mutant integral membrane proteins in the endoplasmic reticulum, posttranslational modification, and purification of recombinant ABCC6/MRP6 proteins in cells using recombinant baculovirus transfer cell expression plasmids. The purpose of this work is protein purification, targeted peptide design, peptide purification, testing of customized monoclonal antibodies, protein expression characterization, enzymatic functional description, structural dynamic range, and primary functional analysis of wild type and mutant proteins.

 

PXE International in the Genetics Community

Sharon and/or Patrick Terry serve on these committees, which give the foundation a central position in the genetics community:

  • President, Genetic Alliance
  • President, Coalition of Heritable Disorders of Connective Tissue
  • Co-Chair, Coalition of Patient Advocates for Skin Disease Research
  • Founder, Co-Chair, Coalition of Advocates for Research on the Eye (CARE)
  • Member, Ad Hoc Committee for Consumer Issues, American Society of Human Genetics
  • Member, Information and Education Committee, American Society of Human Genetics
  • Consumer Representative, Womenís Dermatology Committee, American Academy of Dermatology
  • Representative, Research Council, American Academy of Dermatology
  • Member, Ethical, Legal and Social Issues Research Advisors, National Institutes of Health
  • Member, HapMap Advisory Group, National Human Genome Research Institute, National Institutes of Health
  • Member, Advisory Committee on Informed Consent, Centers for Disease Control, Atlanta, GA
  • Member, Ad Hoc Committee of Experts on IRBs and Informed Consent, HHS Secretary's Advisory Council on Genetic Testing
  • Member, Professional Advisory Board, Aneurysm Outreach Inc.
  • Member, Professional Advisory Board, Autosomal Recessive Polycystic Kidney Disease Alliance
  • Member, Board of Directors, Biotechnology Institute

 

Conclusion

Except for projects supported by grants from the Simmons Foundation and Transgenomic, all PXE International research was funded through private donations. The seeds planted by these small donations have grown into grants from foundations, companies and the government. National Institutes of Health Funding for PXE totaled four million dollars as a direct result of preliminary data gathered with the support of PXE International.

PXE International is in a unique and powerful position to advocate for individuals affected by PXE, and our work is vital to them and to others facing similar struggles. It is the only hope for many individuals who desperately fear blindness. PXE International is also a role model for many other groups throughout the world (Attachment E ñ Keynote from the PXE Gala, Attachment F ñ Researching the Biology of PXE: Partnering in the Process, Terry and Boyd, 2001).

Despite the now millions of dollars we have placed into service on PXE research via the NIH, much remains to be done.  In the United States, the NIH funds basic research.  While this research is critical, we need to move to the next step and look at translating research into treatments.  We have a number of labs ready to work on this ñ it is only up to us to garner the funds to move forward. It is essential, not only to those affected by PXE but also to other groups, to analyze the incredible gold mine of data we have gathered in our search to understand and meet the challenge of PXE. Working into the wee hours of the morning, our fatigue abates through a burning desire to prevent blindness and other difficulties for the thousands of people on our registry. And in so doing, to create a new model of partnership between practitioners and researchers and the individuals they serve.

If this information was helpful to you, please consider making a quick donation today because every penny counts. 100% of donations go to support and research.