Progress of Immunotherapies in Parkinson's Disease.
Progress of Immunotherapies in Parkinson's Disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Zhuzhou, CN · Author affiliation
Department of Neurology, First Affiliated Hospital of Hunan Traditional Chinese Medical College (Hunan Provincial Directly Affiliated Hospital of Traditional Chinese Medicine), Zhuzhou, China.Location evidence
CN · Author affiliation · country only
Science and Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, China.Location evidence
Beijing, CN · Author affiliation
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original abstract
BackgroundImmune dysregulation plays a pivotal role in the pathogenesis and progression of Parkinson's disease (PD). Increasing evidence suggests that immunotherapies targeting α-synuclein (α-syn) pathology may offer potential disease-modifying strategies for PD.ObjectiveThis review aims to systematically summarize recent advances in α-syn-targeted immunotherapies for PD and to evaluate the translational challenges and future directions of precision immunotherapy.MethodsWe critically reviewed the preclinical evidence and clinical trial outcomes of both active immunization strategies, including PD01A and UB-312, and passive monoclonal antibody therapies, such as prasinezumab and cinpanemab.ResultsEarly-phase studies demonstrated favorable safety profiles and robust peripheral target engagement for several immunotherapeutic candidates. However, recent Phase II clinical trials, including PASADENA and SPARK, failed to achieve their primary clinical endpoints, highlighting a substantial gap between biological target engagement and meaningful clinical benefit. Emerging strategies aimed at overcoming these limitations include stage-specific interventions, optimized patient stratification, and differentiated therapeutic approaches.ConclusionAlthough current α-syn-targeted immunotherapies have shown limited clinical efficacy, ongoing advances in precision immunotherapy and individualized intervention strategies may help overcome existing therapeutic bottlenecks. This review provides a strategic framework for the future development of disease-modifying therapies for PD.