title: Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain.
abstract: 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 approximately 900 billion genomic particles (approximately 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.
authors.affiliation: Robert Wood Johnson Medical School-UMDNJ and Cooper Hospital, 08103, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Janson
authors.forename: Scott
authors.initials: S
authors.lastname: McPhee
authors.forename: Larissa
authors.initials: L
authors.lastname: Bilaniuk
authors.forename: John
authors.initials: J
authors.lastname: Haselgrove
authors.forename: Mark
authors.initials: M
authors.lastname: Testaiuti
authors.forename: Andrew
authors.initials: A
authors.lastname: Freese
authors.forename: Dah-Jyuu
authors.initials: DJ
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Shera
authors.forename: Peter
authors.initials: P
authors.lastname: Hurh
authors.forename: Joan
authors.initials: J
authors.lastname: Rupin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Saslow
authors.forename: Olga
authors.initials: O
authors.lastname: Goldfarb
authors.forename: Michael
authors.initials: M
authors.lastname: Goldberg
authors.forename: Ghassem
authors.initials: G
authors.lastname: Larijani
authors.forename: William
authors.initials: W
authors.lastname: Sharrar
authors.forename: Larisa
authors.initials: L
authors.lastname: Liouterman
authors.forename: Angelique
authors.initials: A
authors.lastname: Camp
authors.forename: Edwin
authors.initials: E
authors.lastname: Kolodny
authors.forename: Jude
authors.initials: J
authors.lastname: Samulski
authors.forename: Paola
authors.initials: P
authors.lastname: Leone
mesh_terms: D000581:Amidohydrolases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D017825:Canavan Disease / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D002675:Child, Preschool; D002985:Clinical Protocols; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018579:Patient Selection
chemical_list: D000581:Amidohydrolases; C019751:aspartoacylase