Gene Therapy Platform for Rare Diseases

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

The TRND Program previously initiated a number of collaborations with biotech and academic groups to serve as pilot projects. The overall goal of this effort is to enable TRND to help address challenges in preclinical development, including gene vector design and manufacturing. Advancing these technologies, along with best practices to achieve regulatory approval of gene therapies, will help harmonize preclinical studies and approaches, aiming to improve the speed of development and reduce costs for gene therapy in general. The learnings from the initial projects provided TRND with a robust foundation to contribute to a new NCATS-led initiative, the Platform Vector Gene Therapy (PaVe-GT) pilot project. PaVe-GT seeks to increase the efficiency of clinical trial startup by using the same gene delivery system and manufacturing methods for multiple rare disease gene therapies. This collaborative, trans-NIH initiative includes partners from NCATS, the National Human Genome Research Institute (NHGRI), the National Institute of Neurological Disorders and Stroke (NINDS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). PaVe-GT will develop gene therapies for four diseases: two congenital myasthenic syndromes (Dok7 deficiency; ColQ deficiency) and two organic acidemias (propionic acidemia (PA); cobalamin type B methylmalonic acidemia (MMAB)). All will be based on the adeno-associated virus (AAV)-9 capsid. TRND scientists are conducting the preclinical development necessary to advance all four therapies to clinical testing in patients. To date, a lead AAV-9 gene therapy candidate has been identified for treating PA. Proof of concept studies have demonstrated efficacy of the lead candidate in PA animal models. Bioanalytic assay development is ongoing, and pilot batches of the lead candidate have been manufactured. Scale-up of the product manufacturing process and toxicology studies to demonstrate safety are in the planning phase. The FDA has been engaged to gather early feedback on our development plan for PA. Identification of the lead candidates and animal model studies are in progress for the other three disease indications under the Pave-GT umbrella.