An update on immune-based alpha-synuclein trials in Parkinson’s disease

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...

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Bibliographic Details
Published in:Journal of neurology 2025-01, Vol.272 (1), p.21, Article 21
Main Authors: Alfaidi, Maha, Barker, Roger A., Kuan, Wei-Li
Format: Article
Language:English
Subjects:
alpha-Synuclein - immunology
Antibodies
Antibodies, Monoclonal - pharmacology
Axon guidance
Brain
Clinical trials
Clinical Trials as Topic
Dementia
Dopamine receptors
Drug dosages
Humans
Immune response
Immunization
Immunotherapy - methods
Lewy bodies
Medicine
Medicine & Public Health
Monoclonal antibodies
Movement disorders
Neurodegeneration
Neurodegenerative diseases
Neurological Update
Neurology
Neuroradiology
Neurosciences
Parkinson Disease - drug therapy
Parkinson Disease - immunology
Parkinson's disease
Pathogenesis
Peptides
Substantia nigra
Synuclein
Therapeutic targets
Vaccines
Vaccines - immunology
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Description
Summary: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.
ISSN:0340-5354
1432-1459
1432-1459
DOI:10.1007/s00415-024-12770-x