13 February 2018 - - San Francisco, California-based gene therapy products specialist Audentes Therapeutics, Inc. (NASDAQ: BOLD) has selected an optimized clinical development candidate for its Pompe disease program, a serious, progressive genetic disease characterized by severe muscle weakness, respiratory failure leading to ventilator dependence and, in infants, increased cardiac mass and heart failure, the company said.
Data supporting the selection were presented at the 14th Annual WORLDSymposium 2018 in a poster titled: "A Novel Hybrid Promoter Directing AAV-mediated Expression of Acid Alpha-Glucosidase to Liver, Muscle, and CNS Yields Optimized Outcomes in a Mouse Model of Pompe Disease."
The poster describes the results of an AAV gene therapy construct selection study conducted in a well-characterized mouse model of Pompe disease that evaluated both AAV8 and AAV9 capsid serotypes, paired with novel promoter elements designed to target GAA expression in a range of tissues, including skeletal and cardiac muscle, the nervous system and the liver.
The study included a range of doses and utilized a broad battery of biochemical and immunological assays.
Of the six vectors evaluated, an AAV8 vector with a novel hybrid promoter was selected as the clinical development candidate, AT982. This vector was confirmed to provide GAA expression and activity in target tissues, improved muscle pathology and a favorable immunogenicity profile.
Pompe disease is caused by mutations in the gene encoding the lysosomal enzyme alpha-glucosidase, or GAA, which results in a deficiency of GAA protein and leads to the accumulation of glycogen.
AT982 consists of an AAV8 vector that delivers a GAA gene expression cassette containing a novel hybrid promoter designed to increase GAA activity in targeted tissues, including skeletal and cardiac muscle, the nervous system and the liver.
Audentes is a biotechnology company focused on developing and commercializing gene therapy products for patients living with serious, life-threatening rare diseases. The company has four product candidates in development.