AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial

@article{Lewitt2011AAV2GADGT,
  title={AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial},
  author={Peter A. Lewitt and Ali R. Rezai and Maureen A. Leehey and Steven G. Ojemann and Andrew S. Feigin and S. Tatter},
  journal={The Lancet Neurology},
  year={2011},
  volume={10},
  pages={309-319}
}
Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson's disease.
TLDR
Findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months, with baseline metabolism in the prefrontal cortex correlated with changes in motor UPDRS scores; the higher the baseline PFC metabolism, the better the clinical outcome.
[Gene therapy for Parkinson's disease].
  • S. Muramatsu
  • Biology
    Rinsho shinkeigaku = Clinical neurology
  • 2012
TLDR
The efficacy outcomes are encouraging and indicate that the AAV vector-mediated gene transfer of AADC may benefit advanced PD patients, and a similar approach, delivering A AV vector carrying A ADC gene into the putamen ameliorated the symptoms in children with AADc deficiency.
Parkinson disease: Gene therapy for Parkinson disease shows promise in phase II trial
Delivery of the gene encoding glutamic acid decarboxylase (GAD) improves motor symptoms of Parkinson disease (PD), according to a double-blind, randomized, shamsurgery-controlled phase II study
Long-term follow-up of a randomized AAV 2-GAD gene therapy trial for Parkinson ’ s disease
TLDR
Analysis of all FDG PET images over 12 months revealed significant metabolic declines in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group compared with the sham group.
Of Monkeys and Men: Analysis of the Phase 2 Double-Blind, Sham-Surgery Controlled, Randomized Trial of AAV2-Neurturin Gene Therapy for Parkinson’s Disease
TLDR
The background for this trial includes a sizable literature of animal studies that found that the neurotrophic factors GDNF and its analogue neurturin protect dopaminergic neurons of the substantia nigra pars compacta when exposed to neurotoxins such as 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP).
GAD Gene Therapy for Parkinson’s Disease
TLDR
The development and results of the first human gene therapy for PD used AAV to transfer the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus (STN), which confirmed the effectiveness of AAV-GAD.
Gene-targeting approaches for movement disorders: recent advances.
  • M. Kaplitt
  • Biology, Medicine
    Current opinion in neurology
  • 2019
TLDR
Parkinson's disease gene therapy has moved from purely animal research three decades ago, to initial human studies two decades ago to many applications moving into late stage trials, currently and recent successes and promising new technology should only accelerate the advance of gene therapy into active clinical practice.
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