Editor’s Note: Families facing a rare disease diagnosis often do not know where to turn first in their search for the most advanced treatments and potentially a cure for their children. Only 5 percent of rare diseases have a treatment approved by the Food and Drug Administration, according to the National Organization for Rare Disorders. This is due in part to the lack of high quality biospecimens for research.
Children’s Hospital of Philadelphia Research Institute’s Biorepository Core Facility(BioRC) — which has the capacity for 6 million samples — is uniquely prepared to overcome these challenges by providing investigators with broad access to data-rich biospecimens. In this guest blog appearing on Rare Disease Day®, David Stokes, PhD, technical director for the BioRC, shares examples of how CHOP Research Institute is taking a leading role in biobanking for rare diseases and the ways these services are integral to empowering collaboration and discovery.
Biobanking is the backbone of rare disease research. The simple reason is that biobanks and the infrastructure they’re based on can provide researchers with biospecimens that otherwise would be impossible to obtain on their own, especially in the numbers required to carry out meaningful pediatric research.
In the U.S., rare diseases are those that affect patient populations of 200,000 or less and are comprised of 6,000 to 8,000 different disorders. Many of these disorders have hard-to-pronounce names, obscure origins, and unknown prognoses, but these “one-of-a-kind” kids become familiar faces and a true source of strength and inspiration for our clinician-scientists. By virtue of their world-renowned commitment to personalized medicine and dedication to uncovering the causes of many pediatric rare diseases, over the last decade CHOP has developed and continues to refine a multi-pronged strategy to biobanking.
Biobanking is the collection, storage, annotation, and characterization of bodily fluid or tissue samples from large numbers of people that can be shared with multiple researchers to improve our understanding of health and disease. Obtaining high quality specimens and data would seem simple enough to achieve, but in practice, this process is daunting. When you realize that the specimens are likely to be used for discovery of currently unknown biomarkers with equally unknown stability, obtaining as much pre-analytical data as possible is imperative. Most importantly, the fact that these specimens are from children — some of whom have a devastating and currently incurable rare disease — makes quality control paramount.
The Center for Applied Genomics (CAG), led by Hakon Hakonarson, MD, PhD, has been at the forefront of the Research Institute’s biobanking effort for rare diseases by taking an all-encompassing approach. CAG has collected biospecimens with families’ consent from more than 120,000 children who have visited CHOP. This represents one, if not the largest, unbiased collection of specimens from children with both common and rare pediatric diseases. Within this collection are samples from over 13,000 patients with rare diseases. To date, CAG has identified over 100 novel genes that are associated with or causative of rare diseases in children. Several of these discoveries are undergoing translational work at CAG and development into new and effective therapies that are aimed at reversing the consequences of these gene mutations.
Other rare disease biobanking efforts at CHOP have taken a more targeted but highly collaborative approach. For example, the Children’s Brain Tumor Tissue Consortium (CBTTC), led at CHOP by Phillip “Jay” Storm, MD, and Adam Resnick, PhD, is a multi-institutional effort aimed at supporting research for children with pediatric brain tumors. The 17-member institutions collect specimens from pediatric brain tumor patients — many have rare types of cancer — from across the world under consistent and high quality protocols. The collection is banked right here at CHOP in the BioRC. The CBTTC, in collaboration with Jeffrey Pennington’s and Alex Felmeister’s team in the Department of Biomedical and Health Informatics (DBHi) at CHOP, also have established a highly transparent data sharing infrastructure that allows virtually any researcher to access the de-identified clinical, biospecimen, and research data associated with this collection.
The DBHi’s infrastructure consists of a full suite of tools for open-ended, longitudinal, and diverse temporal tissue biobanking at CHOP. The Biorepository Toolkit allows for clinical, genomic, and imaging associations collected at any time during a biobanking project, all of which become rich annotations for the biospecimens.
The future vision of biobanking at CHOP is aimed at bringing the elements of transparency, collaboration, specimens and data, reliability, and an entrepreneurial spirit together to provide a gateway for all investigators to see and query all of the data associated with banked specimens at CHOP. To do this, CHOP has created an Institutional Biobanking Committee (IBC), headed by Pathologist in Chief Robert Doms, MD, PhD, to establish the groundwork for this vision. The IBC is comprised of stakeholders from multiple departments (clinical, research and informatics) and has established policies to guide CHOP’s future biobanking activities. These tenets include formal institutional oversight, formalized quality assurance and quality control, universal access, and support for additional institutional and investigator-led collection efforts. The BioRC’s dedicated staff is working hard with everyone involved to help make this vision a reality.
While our experts are hard at work behind the scenes to give patients with rare disease hope, their families are on the frontlines putting this hope into action. In May 2016, Angela Waanders, MD, MPH, an attending physician in the Neuro-Oncology Program and the Neurofibromatosis Program at CHOP and a leading member of CBTTC, met with the Gustafson family who founded the Swifty Foundation after losing their son to medulloblastoma. They are funding a two-year pilot initiative to inform a larger national program that will provide an opportunity for families to donate biospecimens for research after a patient dies. This program will be a “game changer,” as it will provide whole brain, spine, blood and cerebral spinal fluid samples that traditionally have been very hard to obtain for research.
On this Rare Disease Day, please pause to recognize and show support for all of the patients and families — in the U.S., that’s 30 million Americans living with a rare disease (about one in 10 people) — who are the true pioneers of rare disease research.
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