title: Global CNS gene transfer for a childhood neurogenetic enzyme deficiency: Canavan disease.
abstract: The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant adeno-associated virus (AAV) vectors.
authors.affiliation: CNS Gene Therapy Center, Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA 19107, USA. Paola.Leone@mail.tju.edu
authors.forename: P
authors.initials: P
authors.lastname: Leone
authors.forename: C G
authors.initials: CG
authors.lastname: Janson
authors.forename: S J
authors.initials: SJ
authors.lastname: McPhee
authors.forename: M J
authors.initials: MJ
authors.lastname: During
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000086:Acetazolamide / Q000627:therapeutic use; D000581:Amidohydrolases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology; D017610:Calcium Compounds; D017825:Canavan Disease / Q000175:diagnosis / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003131:Combined Modality Therapy; D003587:Cytomegalovirus / Q000235:genetics; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000627:therapeutic use; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D020404:Glycerophospholipids / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D007276:Injections, Intraventricular; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D009997:Osmotic Pressure; D010714:Phosphatidylethanolamines; D011296:Prenatal Diagnosis; D011323:Primates; D011401:Promoter Regions, Genetic; D011479:Protamines / Q000008:administration & dosage; D051381:Rats
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000085:Acetates; D017610:Calcium Compounds; D004274:DNA, Recombinant; D020404:Glycerophospholipids; D008081:Liposomes; D009419:Nerve Tissue Proteins; D010714:Phosphatidylethanolamines; D011479:Protamines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D001224:Aspartic Acid; D002784:Cholesterol; C000179:N-acetylaspartate; D000581:Amidohydrolases; C019751:aspartoacylase; D000086:Acetazolamide; C120662:calcium acetate