α-synuclein monoclonal antibodies in Parkinson's disease: A failed promise or unmet potential?

Author: Messak M, Abdelmageed A, Khattab YA, Altalab G, Mandour Y, Shaker O.

Editor's Choice
Journal of the Neurological Sciences | α-synuclein monoclonal antibodies in Parkinson's disease: A failed promise or unmet potential?

Article Link: https://doi.org/10.1016/j.jns.2026.125806

A new review evaluates why monoclonal antibodies (mAbs) targeting α-synuclein have so far failed to demonstrate clinical benefit in Parkinson’s disease (PD), despite strong preclinical promise. Analysing data from five randomised controlled trials, the authors assess safety, pharmacokinetics, central nervous system exposure, and target engagement.

While the trials showed that α-synuclein mAbs were generally safe, phase II studies did not meet primary efficacy endpoints or slow disease progression. Limited blood–brain barrier penetration, uncertain central target engagement, pathological heterogeneity, and late intervention timing are identified as key barriers. The review also highlights the need for more sensitive biomarkers and improved PET imaging tracers to better evaluate treatment effects.

Read the full article for a critical appraisal of current evidence and future priorities for immunotherapy development in Parkinson’s disease.