title: Adeno-associated virus 2-mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of infantile neuronal ceroid lipofuscinosis.
abstract: Infantile neuronal ceroid lipofuscinosis (INCL) is the earliest onset form of a class of inherited neurodegenerative disease called Batten disease. INCL is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Autofluorescent storage material accumulates in virtually all tissues in INCL patients, including the brain, and leads to widespread neuronal loss and cortical atrophy. To determine the efficacy of viral-mediated gene therapy, we injected a recombinant adeno-associated virus 2 vector encoding human PPT1 (rAAV-PPT1) intracranially (I.C.) into a murine model of INCL. INCL mice given four I.C. injections of rAAV-PPT1 as newborns exhibited PPT1 activity near the injection sites and decreased secondary elevations of another lysosomal enzyme. In addition, storage material was decreased in cortical, hippocampal, and cerebellar neurons, and brain weights and cortical thicknesses were increased. These data demonstrate that an adeno-associated virus 2 (AAV2)-mediated gene therapy approach may provide some therapeutic benefit for INCL.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Griffey
authors.forename: Ellen
authors.initials: E
authors.lastname: Bible
authors.forename: Carole
authors.initials: C
authors.lastname: Vogler
authors.forename: Beth
authors.initials: B
authors.lastname: Levy
authors.forename: Praveena
authors.initials: P
authors.lastname: Gupta
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cooper
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sands
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005453:Fluorescence; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009472:Neuronal Ceroid-Lipofuscinoses / Q000473:pathology / Q000628:therapy*; D013869:Thiolester Hydrolases / Q000235:genetics*
chemical_list: D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase