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32 - Disappointing Results of Two Human Trials of Monoclonal Antibodies in Parkinson’s Disease

Published online by Cambridge University Press:  19 January 2024

Daniel Gibbs
Affiliation:
Emeritus of Oregon Health and Science University
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Summary

Like Alzheimer’s disease, Parkinson’s disease is a progressive, neurodegenerative disorder that involves deposits of an abnormal protein in the brain. In Alzheimer’s disease, these abnormal proteins are extracellular beta-amyloid and intraneuronal, hyperphosphorylated tau. In Parkinson’s disease, the neuropathological findings are protein deposits of aggregated alpha-synuclein found primarily within neurons in a part of the brainstem called the substantia nigra but in other locations as well. These clumps of alpha-synuclein are called Lewy bodies.

In the August 4, 2022 issue of the New England Journal of Medicine, we have reports of two phase 2 human trials of monoclonal antibodies directed at alpha-synuclein in subjects with early-stage Parkinson’s disease, prasinezumab and cinpanemab.

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Publisher: Cambridge University Press
Print publication year: 2024

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References

Fields, CR, Bengoa-Vergniory, N, Wade-Martins, R. Targeting alpha-synuclein as a therapy for Parkinson’s disease. Front Mol Neurosci 2019; 12: 299. https://doi.org/10.3389/fnmol.2019.00299 (open access).CrossRefGoogle ScholarPubMed
van Dyck, CH, Swanson, CJ, Aisen, P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med 2023; 388: 921. https://doi.org/10.1056/NEJMoa2212948.CrossRefGoogle ScholarPubMed
Pagano, G, Taylor, KI, Anzures-Cabrera, J, et al. Trial of prasinezumab in early-stage Parkinson’s disease. N Engl J Med 2022; 387: 421432. https://doi.org/10.1056/NEJMoa2202867.CrossRefGoogle ScholarPubMed
Lang, AESiderowf, AD, Macklin, EA, et al. Trial of cinpanemab in early Parkinson’s disease. N Engl J Med 2022; 387: 408420. https://doi.org/10.1056/NEJMoa2203395.CrossRefGoogle ScholarPubMed
Espay, AJ, Okun, MS. Abandoning the proteinopathy paradigm in Parkinson’s disease. JAMA Neurol 2023; 80: 123124. https://doi.org/10.1001/jamaneurol.2022.4193.CrossRefGoogle Scholar

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