Nov. 25, 2014: Partnerships with Patient Groups Accelerate Therapeutic Development

Developing interventions for better human health differs from developing other consumer goods in a fundamental way: Interventions to improve health generally are developed without direct input from the people they are meant to benefit. I believe this odd fact of history is responsible for much of the inefficiency and ineffectiveness of translational science. Imagine for a moment that developers of a new snack food locked themselves away in a lab where the criteria for success were novelty and appeal to fellow developers, but they did not consult any consumers. The result could be an innovative snack food that would delight the developers but taste terrible; no one would buy it. This kind of scenario happens often in intervention development.

Patients — or more broadly, people, because most of us are or eventually will be patients — bring data, insights, connections, priorities and urgency to translational research projects. These cannot all come from professionally trained scientists. (I say “professionally trained” because many patients and families become experts in the diseases affecting them.) To make the most of the enormous value patients can offer, I have challenged NCATS scientists to involve patients from the beginning in every project we do, as full members of the team. The NCATS-supported Rare Diseases Clinical Research Network is a leader in this approach; stay tuned for more in a future message. This month, I want to tell you of remarkable success in the preclinical arena at NCATS enabled by a partnership with patients.

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited disorder of the peripheral nervous system, affecting more than 2.6 million people worldwide. This incurable disease slowly damages the nerve cells leading to the arms, hands, legs and feet and results in pain as well as loss of muscle and sensation. A common form of CMT is caused by abnormally high production of a gene called PMP22; blocking this gene’s over-expression could potentially lead to new treatments. But researchers had never identified a small molecule drug with this sort of activity.

Several years ago, patients in the CMT Association (CMTA) proposed to NCATS a partnership to develop testing systems that would help identify chemical compounds to transform into potential drugs to treat CMT. As part of the partnership, NCATS developed a new assay technique to screen for compounds that lower PMP22 expression. Because translation is a team sport, NCATS scientists accomplished this rapid work by collaborating with researchers at the National Human Genome Research Institute, the University of Wisconsin and Sangamo BioSciences. To create the assay, the scientists used a new technique called genome editing to insert biological tools known as reporter genes into the DNA sequence of PMP22 in cells grown in culture. This technique is more specific than past methods, which inserted reporter genes at random locations into the cell’s DNA. The increased specificity led to discovery of an expanded number of potential treatment targets.

CMTA is only one patient-driven group that has worked closely with NCATS; Center experts have formed collaborative relationships with many other rare disease foundations, including those for Niemann-Pick type C, myotonic dystrophy and chordoma. Hannah’s Hope Fund and Alpha-1 Foundation currently support postdoctoral researchers at NCATS seeking potential treatments for giant axonal neuropathy and alpha-1 antitrypsin deficiency, respectively. And the Michael J. Fox Foundation for Parkinson’s Research is supporting screening with NCATS’ chemical libraries to identify potential treatment compounds.

These collaborative relationships are truly synergistic: The patient groups bring funding, expertise in disease biology and advice on meaningful intervention approaches, and NCATS brings expertise in therapeutic development. The result is a more patient-relevant and efficient route to new treatments — true translational innovation.

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