Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue Human gene therapy. Clinical development Année : 2018

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

Katy Howard
  • Fonction : Auteur
G Scott Ralph
  • Fonction : Auteur
Sarah Mason
  • Fonction : Auteur
Philip C Buttery
  • Fonction : Auteur
Philippe Hantraye
  • Fonction : Auteur
Nicola J Tuckwell
  • Fonction : Auteur
Roger A Barker
  • Fonction : Auteur
Kyriacos A Mitrophanous
  • Fonction : Auteur

Résumé

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.
Fichier principal
Vignette du fichier
palfi-et-al-2018-long-term-follow-up-of-a-phase-i-ii-study-of-prosavin-a-lentiviral-vector-gene-therapy-for-parkinson-s.pdf (252.25 Ko) Télécharger le fichier
Origine Publication financée par une institution
Licence

Dates et versions

hal-04412842 , version 1 (23-01-2024)

Licence

Identifiants

Citer

Stéphane Palfi, Jean Marc Gurruchaga, Hélène Lepetit, Katy Howard, G Scott Ralph, et al.. 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, 2018, 29 (3), pp.148-155. ⟨10.1089/humc.2018.081⟩. ⟨hal-04412842⟩
4 Consultations
7 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More