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
- Discovery of the Gene Associated with PXE
- PXE Health Engagement and Lifestyle Program (PXE HELP) Survey
- Mutation Analysis
- Diagnostic Kit
- Cellular and Molecular Studies
- PXE Research Meeting
- Clinical Study at NIH
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
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.
Figure 2 - Number of Affected in PXE International Registry
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.
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.
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
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 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.
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.
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.