Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain

Christopher Janson, Scott McPhee, Larissa Bilaniuk, John Haselgrove, Mark Testaiuti, Andrew Freese, Dah Jyuu Wang, David Shera, Peter Hurh, Joan Rupin, Elizabeth Saslow, Olga Goldfarb, Michael Goldberg, Ghassem Larijani, William Sharrar, Larisa Liouterman, Angelique Camp, Edwin Kolodny, Jude Samulski, Paola Leone

Research output: Contribution to journalArticlepeer-review

215 Scopus citations


This clinical protocol describes virus-based gene transfer for Canavan disease, a childhood leukodystrophy. Canavan disease, also known as Van Bogaert-Bertrand disease, is a monogeneic, autosomal recessive disease in which the gene coding for the enzyme aspartoacylase (ASPA) is defective. The lack of functional enzyme leads to an increase in the central nervous system of the substrate molecule, N-acetyl-aspartate (NAA), which impairs normal myelination and results in spongiform degeneration of the brain. No effective treatment currently exists; however, virus-based gene transfer has the potential to arrest or reverse the course of this otherwise fatal condition. This procedure involves neurosurgical administration of ∼900 billion genomic particles (∼10 billion infectious particles) of recombinant adeno-associated virus (AAV) containing the aspartoacylase gene (ASPA) directly to affected regions of the brain in each of 21 patients with Canavan disease. Pre- and post-delivery assessments include a battery of noninvasive biochemical, radiological, and neurological tests. This gene transfer study represents the first clinical use of AAV in the human brain and the first instance of viral gene transfer for a neurodegenerative disease.

Original languageEnglish (US)
Pages (from-to)1391-1412
Number of pages22
JournalHuman gene therapy
Issue number11
StatePublished - Jul 20 2002


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