Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.03 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in neutrophils | 0.75 |
| chemistry Open Targets | compounds already reach it: brodalumab | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 5 Parkinson's papers of 941 | 0.76 |
| pathways Reactome | 2 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress IL17RA in microglia; measure IL-1β and TNF release and surface HLA-DR and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).
- Cell type
- microglia
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves IL-1β by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of IL17RA in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- IL17RA in dopamine neurons, braak+0.03 (p 0.947) → -0.42 (p 0.262)receipt 6738
- IL17RA in microglia, braak+0.06 (p 0.888) → +0.09 (p 0.825)receipt 6737
Swarm cases
receipt 6738: IL17RA in dopamine neurons, braak
- power
- full sample -0.31 (p 0.214, n 18), 95% CI -0.68 to +0.19. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.29 (p 0.250, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.38 (p 0.120, n 18). could be the mix.
- skeptic
- leave-one-out range -0.46 to -0.23, sign flips 0; without severely affected donors -0.31 (p 0.214, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IL17RA in dopamine neurons.
case closed: nothing better to follow up.
receipt 6737: IL17RA in microglia, braak
- power
- full sample -0.00 (p 0.997, n 18), 95% CI -0.47 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.03 (p 0.901, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.04 (p 0.888, n 18). could be the mix.
- skeptic
- leave-one-out range -0.13 to +0.10, sign flips 9; without severely affected donors -0.00 (p 0.997, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IL17RA in microglia.
case closed: nothing better to follow up.
Receipts
loading the receipts