Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.05 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in kupffer cells | 0.75 |
| chemistry Open Targets | compounds already reach it: azd4818, bms-817399, ccx354 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 2,054 | 0.82 |
| pathways Reactome | 3 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress CCR1 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 CCR1 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
- CCR1 in microglia, braak-0.04 (p 0.909) → -0.19 (p 0.619)receipt 5457
- CCR1 in dopamine neurons, braak-0.14 (p 0.714) → -0.03 (p 0.947)receipt 5458
Swarm cases
receipt 5458: CCR1 in dopamine neurons, braak
- power
- full sample -0.07 (p 0.781, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.16 (p 0.515, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.15 (p 0.555, n 18). could be the mix.
- skeptic
- leave-one-out range -0.20 to +0.04, sign flips 3; without severely affected donors -0.07 (p 0.781, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CCR1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 5457: CCR1 in microglia, braak
- power
- full sample -0.13 (p 0.609, n 18), 95% CI -0.56 to +0.36. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.13 (p 0.609, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.09 (p 0.715, n 18). could be the mix.
- skeptic
- leave-one-out range -0.29 to -0.01, sign flips 0; without severely affected donors -0.13 (p 0.609, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CCR1 in microglia.
case closed: nothing better to follow up.
Receipts
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