A New Gene Therapy for Parkinson Disease

Summary and Comment |
January 16, 2014

A New Gene Therapy for Parkinson Disease

  1. Michael S. Okun, MD

ProSavin showed promise in a phase 1/2 trial, but safety and efficacy questions remain open.

  1. Michael S. Okun, MD

Parkinson disease (PD) is a progressive neurodegenerative syndrome that affects motor and nonmotor abilities. This manufacturer-funded study addressed the safety, tolerability, and efficacy of bilateral intrastriatal delivery of ProSavin, a lentiviral vector–based gene therapy intended to enhance continuous dopamine production in the brain. The study was a phase 1/2 open-label trial with an open-label follow-up for safety. Fifteen patients with mild-to-moderate PD and a well-documented response to dopamine therapy received low-dose (1·9×107 transducing units [TU]; 3 patients), mid-dose (4·0×107 TU; 6 patients), or high dose (1×108 TU; 6 patients) ProSavin.

The patients were followed for 12 months, during which 54 adverse events potentially related to therapy were reported (3 moderate and the rest mild). The most commonly reported adverse events were on-medication dyskinesias requiring medication reductions (particularly early on with the highest dose) and motor fluctuations. The average score on the Unified Parkinson's Disease Rating Scale (UPDRS) III improved by 32% during the off-medication state at 6 months.


In this small study, a new gene therapy approach was safe and well tolerated. The idea was to make striatal cells “dopamine factories.” Notably, this therapy involved a lentivirus, unlike the traditionally used adenoviruses. Whether this change in vector will prove beneficial remains for future studies to show. Although this was not a transplant trial, one cannot help but be concerned for the emergence of dyskinesia in the off-medication state (runaway dyskinesia). The 12-month follow-up and the sample size were inadequate to conclude that this effect will not occur. The choice of surgical site minimized the possibility of runaway dyskinesia.

The positive change in motor outcomes is good news, but this was an open-label study. The motor outcomes were, disappointingly, much lower than the preoperative levodopa response. For this therapy to be viable, a follow-up study must demonstrate outcomes similar to deep brain stimulation. The data suggest that the highest dose may have the best chance to optimize outcomes in future studies. Even if successful, ProSavin will not treat the many nonmotor and levodopa-resistant symptoms, which are critical to address.

Editor Disclosures at Time of Publication

  • Disclosures for Michael S. Okun, MD at time of publication Grant / research support NIH; National Parkinson Foundation; Michael J. Fox Foundation Editorial boards Parkinsonism and Related Disorders; Tremor and Hyperkinetic Disorders Leadership positions in professional societies National Parkinson Foundation (Medical Director and Ask the Doctor Director); Tourette Syndrome Association (Medical Advisory Board)


Reader Comments (1)

Donnajean Hatch-Sherlock, MSN,RN,FNP Other Healthcare Professional, Internal Medicine, clinic

I agree the study contained a small sampling. It does present optimism of what may become a future treatment of PD.

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