A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson's disease.
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| Abstract |
Gene transfer of dopamine-synthesizing enzymes into the striatal neurons has led to behavioral recovery in animal models of Parkinson's disease (PD). We evaluated the safety, tolerability, and potential efficacy of adeno-associated virus (AAV) vector-mediated gene delivery of aromatic L-amino acid decarboxylase (AADC) into the putamen of PD patients. Six PD patients were evaluated at baseline and at 6 months, using multiple measures, including the Unified Parkinson's Disease Rating Scale (UPDRS), motor state diaries, and positron emission tomography (PET) with 6-[(18)F]fluoro-L-m-tyrosine (FMT), a tracer for AADC. The short-duration response to levodopa was measured in three patients. The procedure was well tolerated. Six months after surgery, motor functions in the OFF-medication state improved an average of 46% based on the UPDRS scores, without apparent changes in the short-duration response to levodopa. PET revealed a 56% increase in FMT activity, which persisted up to 96 weeks. Our findings provide class IV evidence regarding the safety and efficacy of AADC gene therapy and warrant further evaluation in a randomized, controlled, phase 2 setting.
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| Authors | Shin-ichi Muramatsu, Ken-ichi Fujimoto, Seiya Kato, Hiroaki Mizukami, Sayaka Asari, Kunihiko Ikeguchi, Tadataka Kawakami, Masashi Urabe, Akihiro Kume, Toshihiko Sato, Eiju Watanabe, Keiya Ozawa, Imaharu Nakano |
| Journal | Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 18 Issue 9 Pg. 1731-5 (Sep 2010) ISSN: 1525-0024 [Electronic] United States |
| PMID | 20606642 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't) |
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