Gene Therapy: The View from NCATS

The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) was established in December 2011. NCATS mission is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of interventions that improve human health across a wide range of human diseases and conditions. Notably, the “innovative methods and technologies” that are NCATS focus include gene therapy, and the “wide range of human diseases” includes rare diseases, which are a special area of focus for NCATS, and for which gene therapy may have a particularly large impact. In contrast to other institutes and centers at NIH, NCATS does not focus on individual diseases or organ systems, but on what is common among them, and on the common roadblocks and limitations in the translational science process. NCATS defines translation as the process of turning observations in the laboratory, clinic, and community into interventions that improve the health of individuals and the public—from diagnostics and therapeutics to medical procedures and behavioral changes. We define “translational science” as the field of investigation that seeks to understand the scientific and operational principles underlying each step of the translational process. We study translation on a system-wide level, focusing on creative solutions to both scientific and operational problems. A hallmark of NCATS approach to translation is collaboration and team science. The enormous range of disciplines—from target qualification through intervention development to demonstration of clinical efficacy to implementation in the community—means that successful translation requires multidisciplinary teams including individuals from diverse scientific backgrounds, as well as patients and patient advocates, working together. Nowhere is the importance of collaboration and team science seen more clearly than in rare diseases. As we will highlight below, patients and patient advocacy groups (PAGs) are an essential part of collaborative teams, and in many cases are driving rare disease intervention development, including gene therapy. One of the biggest hurdles facing therapeutics development in rare diseases is the sheer number of individual conditions, commonly estimated at around 6000. Well over 90% of these rare conditions have no FDA-approved treatment, and at the current rate of new drug development, hundreds of years will pass before all rare diseases are treatable with a therapy shown to be safe and effective. To address this major challenge, NCATS is particularly interested in “platform”-type approaches that can be readily adapted to multiple diseases. One example is high-throughput screening of all clinically approved drugs1 to find those that can be “repurposed” expeditiously to treat other diseases. Another strategy is to take advantage of expanding knowledge of disease biology, and focus drug development on shared underlying molecular etiologies rather than clinical phenotype.2 Gene therapy approaches, including viral vector-mediated ex vivo or in vivo gene transfer, genome editing, and other nucleic acid therapeutics, are inherent platforms, and of obvious relevance for the treatment of the more than 4000 known rare monogenic disorders. In this editorial, we first consider NCATS support for gene therapy across its different programs, including NCATS new initiatives to establish gene therapy-based platforms for rare diseases. We then highlight some areas and aspects of gene therapy we see as particularly promising and how they relate to NCATS mission and priorities.