2012 Annual Report
4301 Connecticut Ave, NW
Washington, DC 20008
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.
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.
2012 was an important year for pseudoxanthoma elasticum research. Major discoveries included:
- 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-‐mouse.
- 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
- 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
- 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 Meeting
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.
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.
Clinical Trial of Magnesium Supplementation as a Treatment for PXE
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.
Of Special Note
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.
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.
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).
Congratulations to Kim Griffiths and Karolina Perino
Winners of the Health Challenge
Vascular Manifestations of PXE
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.
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.
Biennial Conference – Connect and Learn
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.
Passing the Torch
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.
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.
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
We 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 (firstname.lastname@example.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
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
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]