Alpha-Synuclein Seed Amplification Therapy is a biomarker-driven treatment strategy for Parkinson's disease and related synucleinopathies that uses real-time quaking-induced conversion (RT-QuIC) as both a diagnostic tool and an efficacy readout.
RT-QuIC detects pathologically misfolded alpha-synuclein (α-syn) seeds in CSF[1], enabling early diagnosis and treatment monitoring for therapies targeting alpha-synuclein aggregation.
The therapy aims to neutralize and clear toxic alpha-synuclein aggregates:
| Biomarker | Target | Measurement Method | Expected Change |
|---|---|---|---|
| RT-QuIC | Seed negativity | CSF RT-QuIC | Convert to negative |
| α-syn (CSF) | Increase | ELISA | 50-100% increase |
| pSer129-α-syn | Decrease | ELISA | 30-50% reduction |
| Oligomeric α-syn | Decrease | ELISA | 40-60% reduction |
| DaTscan | Improvement | SPECT | Stabilization |
RT-QuIC is an ultra-sensitive assay that detects minute amounts of misfolded α-synuclein seeds by their ability to seed the aggregation of recombinant α-syn in vitro[1:1]. The assay produces a Thioflavin T fluorescence signal when seeds are present.
| Timepoint | RT-QuIC | CSF α-syn | Motor Assessment |
|---|---|---|---|
| Baseline | Required | Required | Required |
| 6 months | Required | Required | Required |
| 12 months | Required | Required | Required |
| 24 months | Required | Required | Required |
Fairfoul et al. Alpha-synuclein RT-QuIC in PD. Annals of Neurology. 2016. ↩︎ ↩︎
Sano et al. RT-QuIC in DLB. Neurology. 2018. ↩︎ ↩︎
Jang et al. Cinpanemab (BIIB054) in Parkinson's disease. Movement Disorders. 2020. ↩︎
Schweighauser et al. Alpha-synuclein aggregates. Nature. 2018. ↩︎