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The aggregation of alpha-synuclein (\u03b1-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 \u03b1-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 \u03b1-syn. Specifically, UB-312, AFFITOPE PD01A, PD03A and ACI-7104.056 are designed to provoke an immune response against \u03b1-syn (active immunisation), while Prasinezumab and Cinpanemab, MEDI1341 and Lu AF82422 focus on directly targeting \u03b1-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.<\/jats:p>","DOI":"10.1007\/s00415-024-12770-x","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T07:11:34Z","timestamp":1733987494000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["An update on immune-based alpha-synuclein trials in Parkinson\u2019s disease"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1380-9935","authenticated-orcid":false,"given":"Maha","family":"Alfaidi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Li","family":"Kuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"issue":"9","key":"12770_CR1","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1002\/mds.27115","volume":"32","author":"JA Obeso","year":"2017","unstructured":"Obeso JA et al (2017) Past, present, and future of Parkinson\u2019s disease: a special essay on the 200th anniversary of the shaking palsy. 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