＜AAN-JSN Joint Symposium (2)-1-3＞Treatments of Parkinson's Disease: from Medications and Functional Neurosurgeries to gene therapies and cell transplantations
パーキンソン病の遺伝子治療
村松 慎一
自治医科大学内科学講座神経内科学〔〒329―0498 栃木県下野市薬師寺3311―1〕
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.
Full Text of this Article in Japanese PDF (208K)
(臨床神経, 52：896−898, 2012)
key words：アデノ随伴ウイルス，ドパミン，芳香族アミノ酸脱炭酸酵素，Neurtrin，グルタミン酸脱炭酸酵素
（受付日：2012年5月24日）
