Gene Therapy for Canavan's Disease Takes a Step Forward

摘要

Canavans disease (CD) is a rare but devastating pediatric leukodystrophy that causes progressive spongy neurodegen-eration and is invariably fatal in congenital form.The disease is associated with >54 loss-of-function mutations in the enzyme aspartoacylase (ASPA), leads to accumulation of the substrate N-acetyl aspartic acid (NAA) in the brain, and is diagnosed via the presence of NAA aciduria. CD is characterized by dysmyelination, intramyelinic edema (leading to hydrocephalus), and extensive vacuolation of the central nervous system (CNS) white matter. Currently there is no established therapy that affects progression of the disease, and survival is based primarily on improved general medical care. A previous gene therapy attempt using liposome-encapsulated plasmid DNA had shown encouraging although transient decreases in local NAA concentrations in the treated brains, which prompted a gene therapy clinical protocol using recombi-nant AAV serotype 2 (rAAV2) in the hope of better dissemination of the vector and more sustainable NAA reductions.