Gene therapy

Over the last 10 years, there have been major advances in gene therapy approaches for the treatment of PD, several of which have entered human clinical trials.^1,6 These trials have produced some promising results, albeit not consistently.¹

Evidence accumulated thus far indicates that gene therapy that targets multiple brain regions – including the striatum, the subthalamic nucleus, and the substantia nigra – can be both safe and well-tolerated in patients with PD.¹

Several key challenges remain for developing a safe and effective gene therapy.¹ These include, how best to control gene expression, how to determine the optimal target, the optimal dose, and the ideal patient population for future gene therapy trials.¹

References:
1. Allen PJ, Feigin A. Gene-based therapies in Parkinson’s disease. Neurotherapeutics 2014; 11 (1): 60–67.

2. Christine CW, Richardson RM, Van Laar AD, et al. Safety of AADC gene therapy for moderately advanced Parkinson disease: three-year outcomes from the PD-1101 trial. Neurology 2022; 98 (1): e40–e50.

3. Chu Y, Kordower JH. Post-mortem studies of Neurturin gene therapy for Parkinson’s disease: two subjects with 10 years CERE120 delivery. Mov Disord 2023; 38 (9): 1728–1736.

4. Niethammer M, Tang CC, LeWitt PA, et al. Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson’s disease. JCI Insight 2017; 2 (7): e90133.

5. Lim S-Y, Klein C. Parkinson’s disease is predominantly a genetic disease. J Parkinsons Dis 2024; 14 (3): 467–482.

6. Coune PG, Schneider BL, Aebischer P. Parkinson’s disease: gene therapies. Cold Spring Harb Perspect Med 2012; 2 (4): a009431.