Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson's disease

Objective To investigate the safety and tolerability of convection-enhanced delivery of an adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor into the bilateral putamina of PD patients. Methods Thirteen adult patients with advanced PD underwent adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor and gadoteridol (surrogate MRI tracer) coinfusion (450 mu L/hemisphere) at escalating doses: 9 x 10(10) vg (n = 6); 3 x 10(11) vg (n = 6); and 9 x 10(11) vg (n = 1). Intraoperative MRI monitored infusion distribution. Patients underwent UPDRS assessment and [F-18]FDOPA-PET scanning preoperatively and 6 and 18 months postoperatively. Results Adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor was tolerated without clinical or radiographic toxicity. Average putaminal coverage was 26%. UPDRS scores remained stable. Ten of thirteen and 12 of 13 patients had increased [F-18]FDOPA Kis at 6 and 18 months postinfusion (increase range: 5-274% and 8-130%; median, 36% and 54%), respectively. Ki differences between baseline and 6- and 18-month follow-up were statistically significant (P < 0.0002). Conclusion Adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor infusion was safe and well tolerated. Increased [F-18]FDOPA uptake suggests a neurotrophic effect on dopaminergic neurons. (c) 2019 International Parkinson and Movement Disorder Society