Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinsons disease: an open label, phase I trial.

Show simple item record Kaplitt, MG en Feigin, A en Tang, C en Fitzsimons, Helen en Mattis, P en Lawlor, Patricia en Bland, RJ en Young, Deborah en Strybing, K en Eidelberg, D en During, Matthew en 2012-03-20T22:56:57Z en 2007 en
dc.identifier.citation Lancet 369(9579):2097-2105 23 Jun 2007 en
dc.identifier.issn 0140-6736 en
dc.identifier.uri en
dc.description.abstract Background Dopaminergic neuronal loss in Parkinson’s disease leads to changes in the circuitry of the basal ganglia, such as decreased inhibitory GABAergic input to the subthalamic nucleus. We aimed to measure the safety, tolerability, and potential effi cacy of transfer of glutamic acid decarboxylase (GAD) gene with adeno-associated virus (AAV) into the subthalamic nucleus of patients with Parkinson’s disease. Methods We did an open label, safety and tolerability trial of unilateral subthalamic viral vector (AAV-GAD) injection in 11 men and 1 woman with Parkinson’s disease (mean age 58∙2, SD=5∙7 years). Four patients received low-dose, four medium-dose, and four high-dose AAV-GAD at New York Presbyterian Hospital. Inclusion criteria consisted of Hoehn and Yahr stage 3 or greater, motor fl uctuations with substantial off time, and age 70 years or less. Patients were assessed clinically both off and on medication at baseline and after 1, 3, 6, and 12 months at North Shore Hospital. Effi cacy measures included the Unifi ed Parkinson’s Disease Rating Scale (UPDRS), scales of activities of daily living (ADL), neuropsychological testing, and PET imaging with 18F-fl uorodeoxyglucose. The trial is registered with the registry, number NCT00195143. Findings All patients who enrolled had surgery, and there were no dropouts or patients lost to follow-up. There were no adverse events related to gene therapy. Signifi cant improvements in motor UPDRS scores (p=0∙0015), predominantly on the side of the body that was contralateral to surgery, were seen 3 months after gene therapy and persisted up to 12 months. PET scans revealed a substantial reduction in thalamic metabolism that was restricted to the treated hemisphere, and a correlation between clinical motor scores and brain metabolism in the supplementary motor area. Interpretation AAV-GAD gene therapy of the subthalamic nucleus is safe and well tolerated by patients with advanced Parkinson’s disease, suggesting that in-vivo gene therapy in the adult brain might be safe for various neurodegenerative diseases. en
dc.publisher The Lancet Publishing Group en
dc.relation.ispartofseries Lancet en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: en
dc.rights.uri en
dc.title Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinsons disease: an open label, phase I trial. en
dc.type Journal Article en
dc.identifier.doi 10.1016/S0140-6736(07)60982-9 en
pubs.issue 9579 en
pubs.begin-page 2097 en
pubs.volume 369 en
dc.rights.holder Copyright: The Lancet Publishing Group en
dc.identifier.pmid 17586305 en
pubs.end-page 2105 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 75331 en Medical and Health Sciences en Medical Sciences en Pharmacology en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 17586305 en

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