Anti-α-synuclein drug explained

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. Anti-α-synuclein drugs are under development for treatment of Parkinson's disease and other α-synuclein-related diseases. 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. 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.^{[3] [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]}

See also

• Anti-amyloid drugs

Notes and References

1. Noguchi-Shinohara M, Ono K . 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 . June 2023 . 10215 . 37373401 . 10298861 . 10.3390/ijms241210215 . free .
2. Knecht L, Folke J, Dodel R, Ross JA, Albus A . Alpha-synuclein Immunization Strategies for Synucleinopathies in Clinical Studies: A Biological Perspective . Neurotherapeutics . 19 . 5 . 1489–1502 . September 2022 . 36083395 . 9606184 . 10.1007/s13311-022-01288-7 .
3. Zampar S, Di Gregorio SE, Grimmer G, Watts JC, Ingelsson M . "Prion-like" seeding and propagation of oligomeric protein assemblies in neurodegenerative disorders . Front Neurosci . 18 . 1436262 . 2024 . 39161653 . 11330897 . 10.3389/fnins.2024.1436262 . free .
4. Fleming SM, Davis A, Simons E . Targeting alpha-synuclein via the immune system in Parkinson's disease: Current vaccine therapies . Neuropharmacology . 202 . 108870 . January 2022 . 34742741 . 10251253 . 10.1016/j.neuropharm.2021.108870 .
5. Grosso Jasutkar H, Oh SE, Mouradian MM . Therapeutics in the Pipeline Targeting α-Synuclein for Parkinson's Disease . Pharmacol Rev . 74 . 1 . 207–237 . January 2022 . 35017177 . 11034868 . 10.1124/pharmrev.120.000133 .
6. McFarthing K, Rafaloff G, Baptista M, Mursaleen L, Fuest R, Wyse RK, Stott SR . Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update . Journal of Parkinson's Disease . 12 . 4 . 1073–1082 . 2022 . 35527571 . 9198738 . 10.3233/JPD-229002 .