Dual-target gene therapy in Parkinson's disease: a multicenter phase 1 trial.
Dual-target gene therapy in Parkinson's disease: a multicenter phase 1 trial.
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The study site has not been established. Author addresses may differ from where the research occurred.
Shanghai, CN · Author affiliation
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Location evidence
CN · Author affiliation · country only
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.Location evidence
Kunming, CN · Author affiliation
State Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.Location evidence
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Safety and Efficacy Study of Parkinson's Disease Gene Therapy Drug (BBM-P002)
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Original abstract
Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson's disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A 'dual approach' targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector-AAVT42-codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson's disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 .