Provided are
gene therapy vectors, such as adeno-associated
virus (AAV), designed for treatment of mutations in the
Eukaryotic Translation Initiation Factor 2B
Subunit Epsilon (EIF2B5)
gene. The EIF2B5
gene provides instructions for making one of five subunits of the elF2B
protein, specifically the epsilon
subunit of this
protein. Such mutations are associated with a
disease or disorder such as a leukoencephalopathy, a megalencephalic leukoencephalopathy, a leukodystrophy, a
stroke, a
migraine,
epilepsy,
multiple sclerosis (MS), Parkinson's
disease (PD), Alzheimer's
disease (AD), astrogliosis in aging, Huntington's
Disease (HD),
amyotrophic lateral sclerosis (ALS), Alexander disease,
hepatic encephalopathy (HE), AicardinGoutieres syndrome, CLC-2-related disease, oculodentodigital
dysplasia, and / or giant axonal neuropathy. Such leukoencephalopathies or leukodystrophies include, but are not limited to, Vanishing
White Matter Disease (VWM). The disclosed gene therapy vectors provide a EIF2B5 cDNA to a subject in need which results in expression of a
wild type or functional EIF2B5
protein. Also provided is a new
promoter, designated gfa1405, which was designed to target astrocytes and neurons. Thus, compositions, nanoparticles,
extracellular vesicles, exosomes, or vector comprising the gfa1405
promoter and methods of its use are also provided.