An anti-α-synuclein drug, or an α-synuclein inhibitor, is a drug which blocks or inhibits α-synuclein.[1][2] α-Synuclein is a protein which is thought to be involved in the development and progression of α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.[1][2] Anti-α-synuclein drugs are under development for treatment of Parkinson's disease and other α-synuclein-related diseases.[1][2] Examples include the monoclonal antibodies prasinezumab and cinpanemab, which both failed to show effectiveness in slowing the progression of Parkinson's disease in phase 2 clinical trials.[1] Other anti-α-synuclein drugs, like the monoclonal antibody exidavnemab, the α-synuclein vaccines PD01A and PD03A, and the small-molecule α-synuclein misfolding and aggregation inhibitors minzasolmin and emrusolmin, are also under development.[1][3][2][4] Memantine is also being studied as a potential disease-modifying treatment for Parkinson's disease by inhibiting cell-to-cell transmission of α-synuclein and is in a phase 3 trial for this purpose.[5][6]
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edit- ^ a b c d e Noguchi-Shinohara M, Ono K (June 2023). "The Mechanisms of the Roles of α-Synuclein, Amyloid-β, and Tau Protein in the Lewy Body Diseases: Pathogenesis, Early Detection, and Therapeutics". Int J Mol Sci. 24 (12): 10215. doi:10.3390/ijms241210215. PMC 10298861. PMID 37373401.
- ^ a b c d Knecht L, Folke J, Dodel R, Ross JA, Albus A (September 2022). "Alpha-synuclein Immunization Strategies for Synucleinopathies in Clinical Studies: A Biological Perspective". Neurotherapeutics. 19 (5): 1489–1502. doi:10.1007/s13311-022-01288-7. PMC 9606184. PMID 36083395.
- ^ Zampar S, Di Gregorio SE, Grimmer G, Watts JC, Ingelsson M (2024). ""Prion-like" seeding and propagation of oligomeric protein assemblies in neurodegenerative disorders". Front Neurosci. 18: 1436262. doi:10.3389/fnins.2024.1436262. PMC 11330897. PMID 39161653.
- ^ Fleming SM, Davis A, Simons E (January 2022). "Targeting alpha-synuclein via the immune system in Parkinson's disease: Current vaccine therapies". Neuropharmacology. 202: 108870. doi:10.1016/j.neuropharm.2021.108870. PMC 10251253. PMID 34742741.
- ^ Grosso Jasutkar H, Oh SE, Mouradian MM (January 2022). "Therapeutics in the Pipeline Targeting α-Synuclein for Parkinson's Disease". Pharmacol Rev. 74 (1): 207–237. doi:10.1124/pharmrev.120.000133. PMC 11034868. PMID 35017177.
- ^ McFarthing K, Rafaloff G, Baptista M, Mursaleen L, Fuest R, Wyse RK, Stott SR (2022). "Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update". Journal of Parkinson's Disease. 12 (4): 1073–1082. doi:10.3233/JPD-229002. PMC 9198738. PMID 35527571.
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