α-synuclein monoclonal antibodies in Parkinson's disease: A failed promise or unmet potential? - PubMed
5 days ago
- #Parkinson's disease
- #α-synuclein
- #Monoclonal antibodies
- Monoclonal antibodies (mAbs) targeting α-synuclein (α-Syn) in Parkinson's disease (PD) have shown disappointing results in clinical trials.
- Five RCTs (three phase-I and two phase-II) involving 786 participants tested three different mAbs, all demonstrating safety but limited efficacy.
- mAbs showed low CSF concentrations (CSF:Serum = 0.2-0.5%) and insufficient evidence of central target engagement.
- Phase-II trials failed to meet primary efficacy endpoints, with no significant slowing of disease progression.
- Key challenges include late intervention timing, poor BBB permeability, α-Syn pathology heterogeneity, and lack of sensitive tools for target engagement.
- Despite preclinical promise, current limitations hinder clinical translation, necessitating urgent research to address these gaps.