title: [Gene therapy for Parkinson's disease].
abstract: The current clinical trials of gene therapy for Parkinson's disease (PD) are based on three strategies. 1. To restore the local production of dopamine by introducing genes associated with dopamine-synthesizing enzymes into the putamen. 2. To protect nigrostriatal projection by delivering the neurturin gene, a trophic factor for dopaminergic neurons, both in the putamen and the substantia nigra. 3. To modulate the neural activity by transducing the subthalamic nucleus with vectors expressing glutamic acid decarboxylase. A phase I clinical study was initiated in 2007 to determine the safety of intra-putaminal infusion of a recombinant adeno-associated virus (AAV) vector encoding aromatic (L)-amino acid decarboxylase (AADC). All six patients enrolled in the trial showed improvements from baseline in the Unified Parkinson's Disease Rating Scale motor scores in the OFF medication state at 36 months after treatment. Although this trial was a small, open-label study and the use of a non-blinded, uncontrolled analysis limits interpretation, the efficacy outcomes are encouraging and indicate that the AAV vector-mediated gene transfer of AADC may benefit advanced PD patients. A similar approach, delivering AAV vector carrying AADC gene into the putamen ameliorated the symptoms in children with AADC deficiency.
authors.affiliation: Division of Neurology, Department of Medicine, Jichi Medical University.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Muramatsu
mesh_terms: D004298:Dopamine / Q000096:biosynthesis; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D010300:Parkinson Disease / Q000628:therapy*
chemical_list: D004298:Dopamine