AAV9-ADSL

AAV9-ADSL is an investigational gene replacement therapy designed to treat Adenylosuccinate Lyase (ADSL) deficiency, a rare inborn error of purine metabolism. The therapy utilizes a recombinant adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the human ADSL gene. ADSL is a critical enzyme in de novo purine biosynthesis and the purine nucleotide cycle; its deficiency leads to the accumulation of toxic metabolites and neurodevelopmental symptoms such as epilepsy, developmental delay, and autistic behaviors. Developed by researchers at UT Southwestern Medical Center, AAV9-ADSL is administered intrathecally to restore enzyme expression in the central nervous system. Preclinical studies in patient-derived fibroblasts and mouse models have demonstrated restoration of ADSL protein expression and a favorable safety profile.