Alfaidi Maha, Barker Roger A, Kuan Wei-Li
John Van Geest Centre for Brain Repair and Department of Clinical Neuroscience, University of Cambridge, Cambridge, CB2 0PY, UK.
Department of Neurology, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
J Neurol. 2024 Dec 12;272(1):21. doi: 10.1007/s00415-024-12770-x.
Parkinson's disease (PD) is a prevalent, chronic neurodegenerative disorder characterised by the progressive loss of dopaminergic neurons in the substantia nigra and other brain regions. The aggregation of alpha-synuclein (α-syn) into Lewy bodies and neurites is a key pathological feature associated with PD and its progression. Many therapeutic studies aim to target these aggregated forms of α-syn to potentially slow down or stop disease progression in PD. This review provides a comprehensive analysis of recent clinical trials involving vaccines and monoclonal antibodies targeting α-syn. Specifically, UB-312, AFFITOPE PD01A, PD03A and ACI-7104.056 are designed to provoke an immune response against α-syn (active immunisation), while Prasinezumab and Cinpanemab, MEDI1341 and Lu AF82422 focus on directly targeting α-syn aggregates (passive immunisation). Despite some promising results, challenges such as variable efficacy and trial discontinuations persist. Future research must address these challenges to advance disease-modifying therapies for PD around this therapeutic target.
帕金森病（PD）是一种常见的慢性神经退行性疾病，其特征是黑质和其他脑区的多巴胺能神经元进行性丧失。α-突触核蛋白（α-syn）聚集成路易小体和神经突是与帕金森病及其进展相关的关键病理特征。许多治疗研究旨在针对这些聚集形式的α-syn，以潜在地减缓或阻止帕金森病的疾病进展。本综述对近期涉及靶向α-syn的疫苗和单克隆抗体的临床试验进行了全面分析。具体而言，UB-312、AFFITOPE PD01A、PD03A和ACI-7104.056旨在激发针对α-syn的免疫反应（主动免疫），而普拉克索单抗、西潘单抗、MEDI1341和Lu AF82422则专注于直接靶向α-syn聚集体（被动免疫）。尽管取得了一些有前景的结果，但诸如疗效不一和试验中断等挑战依然存在。未来的研究必须应对这些挑战，以围绕这一治疗靶点推进帕金森病的疾病修饰疗法。
