At the end of this month is an annual worldwide event called Rare Disease Day. Its aim is to raise awareness with the general public and decision-makers about rare diseases and their impact on patients’ lives. Orphan/rare diseases are a collection of disorders that affect fewer than 200,000 individuals for any single disease type, yet there are more than 7,000 distinct orphan diseases. In all, over 25 million people in the United States are afflicted by orphan diseases. The Rare Disease Day campaign started in Europe and has progressively spread across the world, with over 70 countries participating last year.
Penn Medicine has been at the forefront of rare disease research for decades, and these efforts – as well as many of its other research and clinical milestones -- are being honored this year as part of the Perelman School of Medicine’s 250th anniversary celebration.
For example, FOP research began almost 30 years ago at Penn. FOP, or fibrodysplasia ossificans progressive, is an extremely rare genetic disorder in which soft connective tissue progressively turns to bone. This endeavor formally started in 1989 with the creation of the FOP Collaborative Research Project, later named The Center for Research in FOP and Related Disorders. “It took our team of researchers and collaborators more than 15 years of diligent effort to unravel the genetic cause of FOP that had been shrouded in mystery for so long,” says Fred Kaplan, MD, the Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine, of the 2006 discovery of the mutation that causes FOP. (That discovery certainly was a milestone in the centuries-old history of FOP. The earliest documented case dates back to the 18th century. British physician John Freke described an adolescent whose diagnosis included swellings throughout his back, in a 1740 paper published in Philosophical Transactions.)
Within the last several years of the current century, Penn Medicine’s contribution to the study of rare diseases has continued apace, with the establishment of many superlative centers. A first-of-its-kind interdisciplinary
Orphan Disease Center (ODC) launched in 2011, with a
focus on discovering novel treatments for rare diseases, for example, lysosomal storage disorders. The
Penn Medicine/CHOP Friedreich’s Ataxia Center of Excellence was established in March 2014 to focus on this movement disorder. And the new Center for Rare Cancers and Personalized Therapy within the Abramson Cancer Center has recently launched.
Two Penn-affiliated staff members, who both live with rare diseases, are at the forefront of this new chapter. David Fajgenbaum, MD, MSc, an adjunct assistant professor of Medicine in the division of Hematology/Oncology, who is battling idiopathic multicentric Castleman disease--a rare and deadly hyperinflammatory disorder--as a patient and physician-researcher, started the Castleman Disease Collaborative Network (CDCN), with the support of immediate past Perelman dean Arthur Rubenstein. In the past year, the CDCN has published a new model of pathogenesis for CD in the journal Blood; established a global strategy for solving the disease; hosted the largest-ever international meeting of CD physicians and researchers and held the first-ever summit for CD patients and loved ones. David has also finalized plans for a global CD patient registry to improve care and accelerate research. And the CDCN has launched its first fundraising campaign, called Castleman Warriors. For all of this, Forbes magazine named Fajgenbaum to their 2015 list of 30 Under 30 in Healthcare.
Another amazing patient-advocate is Emily Kramer-Golinkoff, a project manager at the Penn Social Media and Health Innovation Lab, who has an aggressive, rare form of cystic fibrosis. She has what Orphan Disease Center director Jim Wilson, MD, PhD, calls “ultra rare.” And he should know - Wilson has been studying CF for over 20 years, as well as many other rare diseases and gene-therapy approaches to treat them.
Last month, the ODC co-hosted a symposium on Emily’s rare mutation with Emily’s Entourage, her family’s nonprofit. The meeting was especially timely: a medical student with CF joined First Lady Michelle Obama at the State of the Union Address – when the president first announced his new Precision Medicine initiative to improve effectiveness in the fight against diseases of all kinds – the night before the January 21st symposium.
Together, all of these seemingly disparate efforts signal the start of a new chapter in Penn’s long history with orphan disease research. This is a time of renewed "participatory research," where patients and patient-led foundations like Emily’s Entourage and CDCN, along with the Orphan Disease Center, are the key drivers behind basic research on rare diseases. In this model, patients and foundations proactively push the research agenda by engaging all stakeholders, including scientists, clinicians, pharma, biotech, and venture capital to foster a collaborative approach to research to fast-track clinical breakthroughs.
“On a personal level, although I was initially reluctant to enter the business of vetting and driving research, I quickly learned that if I wanted more research on my rare mutation, it was up to me and my foundation to get it,” says Emily. “Nobody had a bigger vested interest in advancing this research than we did, and the reality was, and remains, that I did not have time to wait for research to unfold on its normal timeline. Already we've made great progress. We co-designed and are funding an innovative drug screening study at UCSF and McGill University on the rare mutations not helped by drugs in the pipeline.” Closer to home, for example, Scott Diamond, PhD, chair of the department of Chemical and Biomolecular Engineering at Penn, has created a cell line from Emily’s blood to facilitate testing possible drugs. And, Kevin Foskett, PhD, chair of the department of Physiology who studies basic biology related to CF, is a scientific advisor to Emily’s Entourage.
ODC is also cohosting symposia on other types of orphan diseases, one later this month on LAM, a deadly lung disease, with Vera Krymskaya, PhD, research associate professor of Medicine in the Pulmonary, Allergy and Critical Care Division. And another will be held in early April on Duchenne muscular dystrophy, with Parent Project Muscular Dystrophy. For much of his career, Lee Sweeney, PhD, ODC’s first director, studied mechanisms that help control muscle function with the hope of gaining a better understanding of ways to thwart muscle deterioration caused by degenerative diseases and age.
ODC will also host its second Million Dollar Bike Ride on Saturday May 9th and has awarded funds to researchers all over the United States on behalf of 13 teams from the first Ride. Individual cyclists rode and raised money for their specific orphan/rare disease foundation, and the funds raised were matched dollar-for-dollar by philanthropic donations, up to $50,000 per team. Monies have gone to fund such projects as a postdoctoral fellow studying familial hypercholesterolemia, evaluating the efficacy and safety of a new drug for congenital hyperinsulinism, and identifying molecular targets for Pitt-Hopkins Syndrome treatments. A complete list of the 2014 Million Dollar Bike Ride grant awardees can be found here.
With such a concentration of energy, expertise, and entrepreneurial spirit, Penn Medicine seems poised to continue making history for rare/orphan diseases for the next 250 years.