AAV-FLnP.ALDH5A1-GAD

AAV-FLnP.ALDH5A1-GAD is an adeno-associated virus (AAV)-mediated gene therapy candidate being investigated for the treatment of drug-resistant epilepsy (DRE). Developed by researchers at Boston Children's Hospital, the therapy utilizes a functional natural promoter (FLnP) from the ALDH5A1 gene (which encodes succinic semialdehyde dehydrogenase) to drive the expression of the human GAD1 gene, which encodes the GAD67 isoform of glutamic acid decarboxylase. GAD67 is the primary enzyme responsible for the synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) from the excitatory neurotransmitter glutamate. By targeting both inhibitory interneurons and astrocytes, the construct aims to restore the excitation-inhibition (E:I) balance in the brain. Preclinical studies in mouse models of pharmacologically-induced recurrent epilepsy have shown that systemic administration of the therapy is well-tolerated and significantly reduces seizure-related mortality without adverse behavioral effects.