AAV-pBr-GAD

AAV-pBr-GAD is an adeno-associated virus (AAV)-mediated gene therapy designed for seizure control in epilepsy. It utilizes a broad cell type promoter (pBr) to drive the overexpression of the human glutamic acid decarboxylase (GAD) enzyme. GAD is the rate-limiting enzyme that catalyzes the conversion of glutamate, the primary excitatory neurotransmitter, into gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter. By increasing GAD levels, the therapy aims to simultaneously reduce excitatory glutamate and enhance inhibitory GABA signaling to suppress seizure activity. In preclinical mouse models, systemic delivery using the PHP.eB capsid demonstrated significant antiepileptic effects and was well-tolerated, showing increased survival and delayed seizure onset in convulsant challenges.