Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease.
Gurruchaga, Jean Marc
Ralph, G Scott
Tuckwell, Nicola J
Mitrophanous, Kyriacos A
Human gene therapy. Clinical development
Mary Ann Liebert
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Palfi, S., Gurruchaga, J. M., Lepetit, H., Howard, K., Ralph, G. S., Mason, S., Gouello, G., et al. (2018). Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease.. Human gene therapy. Clinical development, 29 (3), 148-155. https://doi.org/10.1089/humc.2018.081
Parkinson’s disease is typically treated with oral dopamine replacement therapies, however long term use is complicated by motor fluctuations from intermittent stimulation of dopamine receptors and off-target effects. ProSavin, a lentiviral vector based gene therapy that delivers local and continuous dopamine, was previously shown to be well tolerated in a phase 1/2 first-in-human study, with significant improvements in motor behaviour from baseline at 1 year. Here, patients with Parkinson’s disease from the open-label trial were followed up in the long term to assess the safety and efficacy of ProSavin after bilateral injection into the putamen. 15 patients who were previously treated with ProSavin have been followed for up for 5 years with some having been seen for 8 years. Eight patients received deep brain stimulation at different time points and their subsequent assessments continued to assess safety. Ninety-six drug-related adverse events were reported (87 mild, 6 moderate, 3 severe) of which more than half occurred in the first year. The most common drug-related events were dyskinesias (33 events, 11 patients) and on-off phenomena (22 events, 11 patients). A significant improvement in the defined “off” UPDRS part III motor scores, compared with baseline, was seen at 2 years (mean score 29·2 vs. 38·4, n=14, p<0.05) and at 4 years in 8 out of 15 patients. ProSavin continued to be safe and well tolerated in patients with Parkinson’s disease. Moderate improvements in motor behaviour over baseline continued to be reported in the majority of patients who could still be evaluated up to 5 years of follow up.
Humans, Lentivirus, Parkinson Disease, Treatment Outcome, Follow-Up Studies, Genetic Vectors, Adult, Aged, Middle Aged, Child, Child, Preschool, Female, Male, Genetic Therapy, Drug-Related Side Effects and Adverse Reactions
External DOI: https://doi.org/10.1089/humc.2018.081
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285335
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/