Gene therapy for neurodegenerative diseases using adeno-associated viral vectors that can cross the blood-brain barriers.

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We recently developed AAV vectors that can cross the blood-brain or meningeal-brain barriers. Using these AAV vectors, we have shown beneficial effects in mouse models of neurodegenerative diseases. The early intervention of miR-196a delivered by an AAV vector ameliorated the phenotypes in a mouse model of spinal and bulbar muscular atrophy. A single intracardiac administration of the vector carrying neprilysin gene in a mice model of Alzheimer disease reduced Abeta oligomers, with concurrent alleviation of abnormal learning and memory function. Gene delivery of the RNA-editing enzyme, adenosine deaminase, which acts on RNA 2 (ADAR2) in conditional ADAR2 knockout mice prevented progressive motor dysfunction. These AAV vectors may provide a novel platform for treating neurodegenerative diseases, especially where global transduction of a therapeutic gene into the brain is necessary.