AAV-ALDH5A1

AAV-ALDH5A1 (also known as GAL005) is an investigational adeno-associated virus (AAV)-based gene replacement therapy designed for the treatment of succinic semialdehyde dehydrogenase (SSADH) deficiency, an ultra-rare autosomal recessive neurometabolic disorder. SSADH deficiency is caused by mutations in the ALDH5A1 gene, which impairs the catabolism of gamma-aminobutyric acid (GABA) and leads to the toxic accumulation of GABA and gamma-hydroxybutyrate (GHB). AAV-ALDH5A1 delivers a functional copy of the human ALDH5A1 gene under the control of a native human ALDH5A1 promoter (FLnP) to restore SSADH enzyme activity. The therapy utilizes a novel blood-brain barrier (BBB)-penetrating capsid (such as CapX or AAV-BI-hTFR1) that targets human transferrin receptor 1 (hTfR1) to achieve widespread central nervous system and peripheral tissue transduction following intravenous administration. Preclinical studies in SSADH-deficient mouse models have demonstrated normalization of brain chemistry, reduction of toxic metabolites, and reversal of disease symptoms.

Other names

AAV-ALDH5A1 gene therapyAAV-ALDH-5A1 gene therapyAAV-ALDH 5A1 gene therapyAAV-BI-hTFR1-FLnP-hALDH5A1AAV-BI-hTFR-1-FLnP-hALDH5A1AAV-BI-hTFR 1-FLnP-hALDH5A1AAV-FLnP-ALDH5A1AAV-FLnP-ALDH-5A1AAV-FLnP-ALDH 5A1