Title:
AAV vectors for CNS gene therapy

 

Speaker:
Shin-ichi Muramatsu
Professor, Division of Neurological Gene Therapy, Open Innovation Center, Jichi Medical University
Visiting Professor, Center for Gene & Cell Therapy, The Institute of Medical Science, The University of Tokyo

 

Abstract:
Since its discovery in 1965 and characterization in 1983, adeno-associated virus type 2 (AAV2), a prototype of primate AAV, has been a widely used tool in basic neuroscience research and for AAV vector-based gene therapy. AAV2 vectors, when delivered into the brain parenchyma, efficiently transduce neurons and express therapeutic genes for a prolonged period without any significant toxic effects. In clinical studies on advanced Parkinson’s disease, investigators, including us, have shown the motor symptoms to be ameliorated along with an increased dopaminergic activity on positron emission tomography after the gene delivery of aromatic L-amino acid decarboxylase (AADC) into the putamen. The beneficial effects of AADC gene transfer have also been shown in children with AADC deficiency. In our clinical study, motor function was shown to be remarkably improved in all patients with differing degrees of disease severity. Recently, novel AAV vectors have been generated which can achieve global transduction of the central nervous system by intravenous or intrathecal injection. We have been developing gene therapy for various diseases including Alzheimer disease, sporadic amyotrophic lateral sclerosis, spinocerebellar ataxia 1, spinocerebellar ataxia 6, spinal bulbar muscular atrophy, glucose transporter 1 deficiency, and GM2 gangliosidosis using the tyrosine-mutant form of AAV9.

 

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