AAV9P31-gfa2-MLC1

AAV9P31-gfa2-MLC1 is a preclinical gene therapy candidate designed for the treatment of megalencephalic leukoencephalopathy with subcortical cysts (MLC), specifically the MLC1-deficient subtype. The construct utilizes a blood-brain barrier-penetrant adeno-associated virus serotype 9 variant (AAV9P31) to deliver a functional human MLC1 gene. Expression is driven by the astrocyte-specific gfa2 promoter to ensure selective protein restoration in astrocytes, the primary cell type affected in MLC. In mouse models, systemic administration of this vector has demonstrated the ability to reverse brain edema, abolish white matter vacuolation, and normalize motor performance. The therapy aims to restore the MLC1-GlialCAM complex, which is essential for maintaining ion and water homeostasis in the central nervous system.