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.