Gene Therapy for Parkinson's Disease: Preclinical Evaluation of Optimally Configured TH:CH1 Fusion for Maximal Dopamine Synthesis.
MPTP primate model
Parkinson’s disease
dopamine replacement
gene therapy
lentiviral vector
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
13 Sep 2019
13 Sep 2019
Historique:
received:
19
11
2018
accepted:
08
07
2019
entrez:
14
8
2019
pubmed:
14
8
2019
medline:
14
8
2019
Statut:
epublish
Résumé
A recent phase I-II, open-label trial of ProSavin, a lentiviral vector delivering the key enzymes in the dopamine biosynthetic pathway to non-dopaminergic striatal neurons, demonstrated safety and improved motor function in parkinsonian patients. However, the magnitude of the effect suggested that optimal levels of dopamine replacement may not have been achieved. OXB-102, a lentiviral vector with an optimized expression cassette for dopamine biosynthesis, has been shown to achieve a significantly higher dopamine yield than ProSavin. We assessed the efficacy of OXB-102 in the MPTP macaque model of Parkinson's disease (PD). At 6 months post-vector administration, all treated animals showed significant improvements in clinical scores and spontaneous locomotor activity compared to controls, with the highest recovery observed in the OXB-102 high-dose (HD) group. Positron emission tomography quantification of 6-[
Identifiants
pubmed: 31406701
doi: 10.1016/j.omtm.2019.07.002
pii: S2329-0501(19)30073-7
pmc: PMC6685641
doi:
Types de publication
Journal Article
Langues
eng
Pagination
206-216Références
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