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Neurology. 2008 May 20;70(21):1980-3. doi: 10.1212/01.wnl.0000312381.29287.ff. Epub 2008 Apr 9.

Results from a phase I safety trial of hAADC gene therapy for Parkinson disease.

Author information

  • 1Department of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. jleberling@lbl.gov

Abstract

BACKGROUND:

In a primate model of Parkinson disease (PD), intrastriatal infusion of an adeno-associated viral (AAV) vector containing the human aromatic l-amino acid decarboxylase (hAADC) gene results in robust gene expression. After gene transfer, low doses of systemically administered l-dopa are converted to dopamine in the transduced striatal neurons, resulting in behavioral improvement without the side effects typically associated with higher doses of l-dopa. These studies led to the initiation of a phase I safety trial. Here we report the findings for the first cohort of five patients.

METHODS:

Patients with moderate to advanced PD received bilateral infusion of a low dose of the AAV-hAADC vector into the putamen. PET scans using the AADC tracer, 6-[18F]fluoro-l-m-tyrosine (FMT), were performed at baseline and at 1 and 6 months after infusion as an in vivo measure of gene expression.

RESULTS:

PET results showed an average 30% increase in FMT uptake (K(i)(c)) in the putamen after gene transfer. Preliminary analysis of clinical data indicates a modest improvement, but absence of a control and the nonblinded analyses make interpretation difficult.

CONCLUSIONS:

Thus far, this gene therapy approach has been well tolerated and shows PET evidence of sustained gene expression. These initial findings demonstrate the safety of the therapy; higher doses of adeno-associated viral vector containing the human aromatic l-amino acid decarboxylase gene in the next cohort of patients may further increase dopamine production in the putamen and provide more profound clinical benefit.

PMID:
18401019
[PubMed - indexed for MEDLINE]
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