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Hum Gene Ther Clin Dev. 2018 Sep;29(3):148-155. doi: 10.1089/humc.2018.081.

Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease.

Author information

1
1 AP-HP, Groupe Hospitalier Henri-Mondor , DHU PePsy, Neurochirurgie, Psychiatrie Créteil, France .
2
2 Université Paris 12 , Faculté de Médecine, IMRB INSERM U 955 Team 14 Créteil, France .
3
3 Oxford BioMedica Ltd. , Oxford, United Kingdom .
4
4 John van Geest Centre for Brain Repair, Department of Clinical Neuroscience, Addenbrooke's Hospital , Cambridge, United Kingdom .
5
5 CEA, DSV FBM, MIRCen and CNRS URA2210, Fontenay-aux-Roses , France .

Abstract

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 I/II first-in-human study, with significant improvements in motor behavior 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. Fifteen patients who were previously treated with ProSavin have been followed for up to 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" Unified Parkinson's Disease Rating Scale part III motor scores, compared to baseline, was seen at 2 years (mean score 29 · 2 vs. 38 · 4, n = 14, p < 0.05) and at 4 years in 8/15 patients. ProSavin continued to be safe and well tolerated in patients with Parkinson's disease. Moderate improvements in motor behavior over baseline continued to be reported in the majority of patients who could still be evaluated up to 5 years of follow-up.

KEYWORDS:

Parkinson's disease; dopamine; gene therapy; lentiviral vector

PMID:
30156440
PMCID:
PMC6157351
DOI:
10.1089/humc.2018.081
[Indexed for MEDLINE]
Free PMC Article

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