Gene Therapy Platform for Rare Diseases

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

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 has begun 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, and an Orphan Drug Designation (ODD) has been received for the AAV9-hPCCA gene therapy product. Identification of the lead candidates, animal model natural history studies, and proof of concept studies are in progress for the other three disease indications under the Pave-GT umbrella. In addition, a new collaboration with the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) is being established for development of an open access platform for AAV production. Dissemination efforts include drafting a white paper to outline the regulatory process for obtaining an ODD. Additional dissemination activities are in progress and are geared towards creating a preclinical playbook outlining the gene therapy drug development process.