Gene Therapy for PD (AAN 2006)

Subject: Gene Therapy for PD (AAN 2006)

Date: 4/18/2006

E-MOVE reports from the 58th Annual Meeting of the American Academy of Neurology, San Diego California, April 1-8, 2006. Poster, session, and page numbers are from Neurology 2006;66 (supplement 2)

1. Early results from a clinical trial of AADC gene therapy for Parkinson's disease
JE Eberling, KS Bankiewicz, D McGuire, M Aminoff, C Christine, P Starr, P Larson, W Jagust
P05.063, A276

2. Aromatic L-amino acid decarboxylase gene transfer therapy for Parkinson's disease: Initial results of an open-label, dose-escalation, safety and tolerability study
CW Christine, PA Starr, P Larson, R Mah, J Eberling, W Jagust, D McGuire, MJ Aminoff
S23.005, A185

Four patients with average disease duration of 14 years received treatment with adeno-associated virus carrying the gene for aromatic amino acid decarboxylase bilaterally to the putamen. AADC converts levodopa to dopamine. PET with the AADC tracer fluoro-L-m-tyrosine (FMT) showed an increase in uptake at 1 month (12% left, 42% right) in 4 patients, and slightly less uptake at 6 months (10% left, 33% right). Average UPDRS motor score at baseline was 41.3 off and 16.2 on, which remained unchanged at the 6-month visit.

Supported by Avigen

3. Gene therapy for Parkinson's disease with AAV-GAD: FDG PET results
A Feigin, C Tang, Y Ma, V Dhawan, M During, M Kaplitt, D Eidelberg
P01.146, A48

Eleven patients received treatment with adeno-associated virus carrying the glutamic acid decarboxylase gene delivered unilaterally to the subthalamic nucleus. The treatment was meant to increase GAD expression, increase synthesis of the inhibitory neurotransmitter GABA, and reduce STN output. After 6 months, UPDRS off motor score declined from 38.9 to 29.8 (p<0.03). FDG PET revealed decreased brain metabolism in Gpi and ventrolateral thalamus on the treated side, and no significant changes on the untreated side.

Supported by Neurologix

4. Phase 1 study of putaminal gene transfer with adeno-associated virus serotype-2[AAV2]-neurturin [NTN] (CERE-120) for Parkinson's disease: Preliminary observations
WJ Marks, LA Verhagen-Metman, PA Starr, PS Larson, RA Bakay, R Taylor, D Cahn-Weiner, RT Bartus, JL Ostrem
S23.006, A185

Twelve PD patients with average disease duration of 11 years received treatment to the putamen with adeno-associated virus carrying the gene for neurturin, a growth factor related to GDNF and shown in experimental models to protect dopaminergic neurons from degeneration. Six patients received a low dose and 6 a high dose (1.4 x 10^11 vs. 5.7 vector genomes). Preliminary analysis showed that no serious adverse effects have occurred, although one patient experienced transient dyskinesia.

Supported by Ceregene