NEW SOW FOR REGULATORY ACTIVITIES FOR PCCA AND MMAB GENE THERAPY PRODUCTS

Ccs Associates, Inc., San Jose CA

Investigators

Abstract

The Division of Preclinical Innovation (DPI) at National Center for Advancing Translational Sciences (NCATS) conducts translational research in human therapeutics development. NCATS aims to make gene therapy development and clinical testing more streamlined, more efficient, and potentially more accessible to many people with rare disease. With this aim, NCATS in collaboration with National Human Genome Research Institute (NHGRI) and National Institute of Neurological Disorders and Stroke (NINDS) has initiated the Platform Vector Gene Therapy (Pave-GT) project. PaVe-GT includes development of gene therapy treatments for four diseases: two congenital myasthenic syndromes (CMS) and two organic acidemias (OA). Organic acidemias (OAs) are a group of inherited metabolic disorders, which disrupt branch chain amino acid, odd-chain fatty acid and/or cholesterol metabolism and cause a buildup of organic acids in the blood. Methylmalonic acidemia (MMA), propionic acidemia (PA), isovaleric acidemia and glutaric acidemia type 1, are examples of OAs, with MMA and PA collectively representing the most common of the OAs. Typically, patients with OAs present during the newborn period with a “crisis,” most commonly in the form of a life-threatening episode of metabolic acidosis and high ammonia. In the United States, most patients with OAs are detected by newborn screening. The type of OA, such as MMA or PA, can be identified by the presence of specific organic acids in blood or urine, with the exact cause determined by genetic testing. The current therapy for patients with OAs includes dietary restriction of amino acids, special formulas, carnitine supplementation and, in some patients with MMA, vitamin B12 given by injections. Severely affected patients may receive a liver transplant to increase the hepatic enzymatic activity. In general, the long-term clinical outcomes for OAs are poor, and there is a great need for new treatment options.