Deep brain stimulation is well tolerated and effective following ProSavin® gene therapy for Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder initially treated with oral dopaminergic medications. When motor fluctuations and side effects develop on these treatments, Deep Brain stimulation (DBS) of the subthalamic nucleus (STN) is used. Striatal dopamine replacement, using a lentiviral vector-based gene therapy (GT), was previously shown to be well-tolerated, leading to clinical improvement in motor function. Later, some of these patients showed evidence of disease progression and were proposed DBS since new GT injection was not yet authorized by regulatory authorities. The tolerance and motor efficacy of DBS in this cohort is reported. Eight patients who had previously received GT (GT/DBS group), were evaluated pre- and 12 months-post DBS. A control group of 84 PD patients who had received DBS, were used for comparison (DBS group). Patients in the GT/DBS group were administered DBS significantly later after PD diagnosis than the DBS group (19.6 vs 12.1 years). Similar rate of serious adverse events, UPDRS III MEDSOFF scores 12 months post-DBS and reduction in LEDD between baseline DBS and 12 months post DBS were reported in both groups. The decrease in axial scores from UPDRS III MEDSOFF/STIMON at 12 months post-DBS compared with baseline DBS was significantly greater in the GT/DBS group than in the DBS group. DBS of the STN was as effective and well-tolerated in GT/DBS PD patients as in the DBS group, even when administered later in their disease course.