Oct. 8, 2014: Integration Expands Opportunities to Understand and Treat Rare Diseases

I often talk about how NCATS’ mission and programs are different from other organizations in the research ecosystem. One of these differences is that NCATS is “disease-agnostic”: rather than focusing on a single type of condition or biological system, we look for what is common among diseases and the translational process. This approach acknowledges that seemingly different conditions can share underlying molecular causes, and it has the potential to greatly accelerate the development of health-improving interventions, including those that treat more than one disease.

This systematic approach is especially important for investigating rare diseases, which number in the thousands; only a few hundred have treatments approved by the Food and Drug Administration. Although rare diseases by definition affect relatively small numbers of people (defined as fewer than 200,000 people in the U.S.), together these diseases affect an estimated 25 million Americans and are the source of enormous suffering, premature death and lost economic activity. Mutations in single genes cause most rare diseases, but these mutations typically affect many different organ systems simultaneously. The large number of currently untreatable rare diseases and their effects on multiple organs make the typical one-disease-at-a-time, one-organ-at-a-time translational model untenable.

Enter the Rare Diseases Clinical Research Network (RDCRN), an NCATS-led initiative with an aim to address many of the unique challenges in developing rare disease therapies, including difficulties in diagnosis, widely dispersed patients and scientific experts, and a perceived high risk and cost for developing such treatments. Established in 2003, the RDCRN supports consortia of medical research centers that work together to investigate groups of related rare diseases, including performing long-term natural history studies and clinical trials of new medications. The RDCRN develops robust data on more than 200 rare conditions, enabling scientists to better understand and learn from the common features among diseases.

I am pleased to announce that on Oct. 8, 2014, NIH announced nearly $29 million in awards to expand the RDCRN to support 22 consortia and a Data Management and Coordinating Center (DMCC). The network is a distinctive clinical research entity that exemplifies fundamentals of the NCATS mission:

  • Collaboration: Multidisciplinary scientists from 240 institutions work together to conduct multisite studies, of which 91 are currently active and enrolling patients.
  • Patient and community engagement: Nearly 100 patient advocacy groups have partnered with consortia to assist in patient recruitment, study design, information dissemination and young scientist training.
  • Training: Young scientists receive mentoring and guidance in conducting research on rare diseases.
  • Central data collection and storage: A DMCC provides the resources to pool data from RDCRN studies in a single location so that researchers can access information more easily and find links among diseases.

A recent success from the RDCRN-supported Urea Cycle Disorders Consortium illustrates the kind of outcomes these consortia can produce. Urea cycle disorders (UCDs) are caused by genetic defects that render the body unable to remove ammonia from the blood. Ammonia is toxic and can damage organs, including the brain. Scientists have discovered a number of UCDs, all caused by defects in different genes but related by the biochemical pathway they affect and the symptoms they cause. By tackling UCDs as a group rather than individually, the UCD Consortium team catalyzed the development and approval of three drugs to treat UCDs, giving patients treatments for these life-threatening conditions.

You can follow the RDCRN’s successes on the NCATS website, where you also can learn more about the critical role of patients in each of the consortia. The RDCRN showcases an integrated approach to disease translation that also promises to provide insights into optimal translational methods as well as causes and treatments of rare and common diseases. In my “3 D’s” parlance, the RDCRN developed innovative approaches and demonstrated their success in individual rare diseases, and now NCATS is actively disseminating those approaches to the research community to advance our goal of delivering more treatments to more patients more quickly.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences