Parkinson's disease gene therapy: a comparative effectiveness review of completed clinical trials in terms of their possible implementation in treatment

Abstract

Background: Parkinsons disease (PD) is a neurodegenerative disease in which dopaminergic neurons are damaged, and Lewy bodies accumulate in the brain, leading to both motor and non-motor symptoms. Currently, no treatment is available to slow down or reverse disease progression. The need to find new solutions has prompted research interest in gene therapy. Aim of the study: The purpose of this review is to analyze a selection of completed clinical trials on gene therapy in PD and their possible implementation in treatment. Material and Methods: Clinical trials were selected from the ClinicalTrials.gov database using the following search criteria: Parkinsons disease, gene therapy, and completed status. Trials that were ongoing, terminated, preclinical, or with different research subjects were excluded. PubMed and Google Scholar databases were also searched for neuropathology, symptoms, and treatment recommendations for PD. The results of reviewed clinical trials have been checked in terms of the efficacy and safety of the investigated therapies in the treatment of PD. Results: We analyzed 7 completed clinical trials, namely VY-AADC01 (NCT01973543), AAV-GAD (NCT00195143), ProSavin (NCT00627588), AAV2-GDNF (NCT01621581), CERE-120 (NCT00252850), VY-AADC01 (NCT03065192), and CERE-120 (NCT00985517) with a total of 152 patients. Five of the studies had published results and four of these five had satisfactory results. VY-AADC01, AAV-GAD, and CERE-120 were found to be safe and potentially effective in the treatment of PD, while ProSavin demonstrated insufficient effectiveness. Conclusions: There is limited available data regarding completed clinical trials for PD gene therapy, with a small number of patients, making it difficult to give a final statement on the possibility of using gene therapy to treat PD. However, the clinical trials reviewed herein show promising results with the potential to revolutionize the treatment of PD.