Winston, G; Kharas, N; Svenningsson, P; Jha, A; Kaplitt, MG; (2025) Gene therapy for Parkinson's disease: trials and technical advances. The Lancet Neurology , 24 (6) pp. 548-556. 10.1016/S1474-4422(25)00125-5.

Text THELANCETNEUROLOGY-D-24-00918_R1-2_merged.pdf - Accepted Version Access restricted to UCL open access staff until 21 November 2025. Download (1MB)

Abstract

Gene therapy has long held promise as a method for targeted alteration of neuronal function in Parkinson's disease. Different gene-therapy approaches aim to correct dysfunctional circuits or have attempted to protect vulnerable neurons to slow disease progression. Clinical trials have used viral vectors to deliver genes either directly into brain regions through stereotaxic injection or globally through infusion into the CSF of the cisterna magna. Bilateral delivery of GAD into the subthalamic nucleus has resulted in some clinical improvements, and the delivery into the putamen of genes that codify for enzymes involved in dopamine synthesis has resulted also in some improvements. Growth factor gene therapy has been the focus of several studies, with both imaging and neuropathological evidence of gene expression and possible neuroprotection. An ongoing trial of gene therapy to correct mutated GBA in patients with Parkinson's disease and GBA mutations is the first to use gene therapy to try to correct a genetic cause of Parkinson's disease in human beings. Technical advancements in vector delivery, such as novel capsids and the disruption of the blood-brain barrier by use of focused ultrasound, will help advance gene therapy in Parkinson's disease.

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