AAV9fyhr-PDHA1

AAV9fyhr-PDHA1 is an investigational gene therapy designed to treat Pyruvate Dehydrogenase Complex Deficiency (PDCD), a rare genetic mitochondrial disorder primarily caused by mutations in the X-linked PDHA1 gene. The therapy consists of an optimized PDHA1 transgene packaged within AAV9fyhr, an enhanced adeno-associated virus serotype 9 (AAV9) variant. This specific capsid variant was engineered to provide approximately three times higher transduction efficiency in the central nervous system of both mice and non-human primates following intrathecal delivery compared to standard AAV9. Developed by researchers at UT Southwestern Medical Center, the therapy aims to restore pyruvate dehydrogenase complex (PDC) enzyme activity, thereby normalizing oxidative metabolism, reducing elevated serum lactate levels, and improving neurological and neuromuscular function. Preclinical data in a knock-in mouse model (E75A) have demonstrated that intrathecal administration improves locomotor activity and biochemical disease markers without significant safety concerns.

Other names

AAV9fyhr-based PDHA1 gene therapyAAV-9fyhr-based PDHA1 gene therapyAAV 9fyhr-based PDHA1 gene therapy