Sunday, January 05, 2020 1:46:39 PM
Badin RA1,2, Binley K3, Van Camp N1,2, Jan C1,2, Gourlay J1,2, Robert C1,2, Gipchtein P1,2, Fayard A1,2, Stewart H3, Ralph GS3, Lad Y3, Kelleher M3, Loader J3, Hosomi K4,5, Palfi S4,5, Mitrophanous KA3, Hantraye P1,2.
Author information
1
CEA, DRF, Institute of Biology François Jacob, Molecular Imaging Research Center (MIRCen), 92265 Fontenay-aux-Roses, France.
2
CNRS, CEA, Paris-Sud University, Université Paris-Saclay, Neurodegenerative Diseases Laboratory (UMR9199), 92265 Fontenay-aux-Roses, France.
3
Oxford Biomedica, Windrush Court, Transport Way, Oxford OX4 6LT, UK.
4
AP-HP, Groupe Hospitalier Henri-Mondor, DHU PePsy, Neurochirurgie, Créteil, 94010, France.
5
Université Paris 12, Faculté de Médecine, IMRB, INSERM U955, Team 14, Créteil 94010, France.
Abstract
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-[18F]-fluoro-L-m-tyrosine uptake showed a significant increase in amino acid decarboxylase activity for all treated animals, compared with controls, where the OXB-102 HD group showed the highest level of dopaminergic activity. A toxicology study in macaques demonstrated that the vector was safe and well tolerated, with no associated clinical or behavioral abnormalities and no immune response mounted against any transgene products. Overall, these data support the further clinical development of OXB-102 for the treatment of PD.
Full paper at the link below:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685641/
Good luck and GOD bless,
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