The NIH has awarded grants to six medical centers around the country to select from the most difficult-to-solve medical cases and together develop effective approaches to diagnose them. The new clinical sites added to the NIH Undiagnosed Diseases Network (UDN) will conduct clinical evaluation and scientific investigation in cases that involve patients with prolonged, undiagnosed conditions.
Each clinical site will contribute local medical experience to the NIH UDN. The network includes and is modeled after an NIH pilot program that has enrolled people with intractable medical conditions from nearly every state, the District of Columbia and seven foreign countries. The network builds on a program at the NIH Clinical Center in Bethesda, Md., that for the past six years has evaluated hundreds of patients and provided many diagnoses, often using genomic approaches, for rare conditions.
“Newly developed methods for genome sequencing now provide us amazingly powerful approaches for deciphering the causes of rare undiagnosed conditions,” said Eric D. Green, M.D., Ph.D., director of the National Human Genome Research Institute. “Along with robust clinical evaluations, genomics will play a central role in the UDN’s mission.” Green and Story Landis, Ph.D., director of the National Institute of Neurological Diseases and Stroke, co-chair the UDN working group.
Undiagnosed diseases are conditions that even skilled physicians cannot diagnose despite extensive clinical investigation. They may not be recognized by doctors because they are rarely seen, are previously undescribed or are rare forms of more common diseases.
The NIH Common Fund awarded four-year grants of approximately $7.2 million (pending available funds) to each of the six medical centers. James M. Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), announced in an NIH telebriefing that the six newly awarded sites join a clinical site already established at the NIH in pursuing cutting-edge diagnoses. In addition, this past December, the NIH selected Harvard Medical School as the UDN Coordinating Center for the multi-institution network.
“The NIH Undiagnosed Diseases Network has the potential to transform medicine and serve as a catalyst for new discoveries,” said Anderson. “It is an ideal NIH Common Fund program—the only one focused on diagnoses of rare disorders.”
The following institutions were awarded grants to establish UDN clinical sites:
William A. Gahl, M.D., Ph.D., clinical director at the National Human Genome Research Institute (NHGRI), director of the NIH-based Undiagnosed Diseases Program (UDP) and co-coordinator of the UDN working group, said, “Often, patients have a lot of physical complaints and no objective diagnoses. Our goal is to use the latest tools to make a diagnosis that spans the clinical, pathological and biochemical spectrum to uncover the basic genetic defect.”
Since 2008, the UDP has explored this area of medical research and acquired practical insights in the process of enrolling approximately 600 undiagnosed children and adults in its clinical protocols. The multidisciplinary clinical and research team diagnosed approximately 100 patients (20%-25% of those evaluated), discovered two unknown diseases and identified 15 genes not previously associated with any other human disease. A combination of genomic and clinical analyses contributed to the diagnoses.
By including an additional six clinical sites, the NIH UDN will both draw upon the unique experience of new clinical research groups and cultivate opportunities for collaboration among a larger group of expert laboratory and clinical investigators. Physicians within the network will collect and share high-quality clinical and laboratory data, including genomic information, clinical observations and documentation of environmental exposures. They also will benefit from common protocols designed to improve the level of diagnosis and care for patients with undiagnosed diseases.
“The UDN will look at diseases across all clinical specialties using new tools and methods of analysis for the identification of new diseases,” said Anastasia L. Wise, Ph.D., a program director in NHGRI's Division of Genomic Medicine and co-coordinator of the UDN working group that oversees the development and implementation of the UDN. “The network will facilitate collaboration and shared use of genomic tools among the sites.”