Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in breast lactating cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 1 pathway; mostly immune signalling | 0.90 |
Knock down and overexpress CNTFR in astrocytes; measure IL-1β and TNF release and surface HLA-DR and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- 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 CNTFR in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CNTFR in astrocytes, braak-0.37 (p 0.323) → +0.55 (p 0.122)receipt 13578
- CNTFR in dopamine neurons, braak-0.43 (p 0.251) → -0.09 (p 0.821)receipt 13579
Swarm cases
receipt 13579: CNTFR in dopamine neurons, braak
- power
- full sample -0.23 (p 0.365, n 18), 95% CI -0.63 to +0.27. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.30 (p 0.221, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.55 (p 0.018, n 18). not the mix.
- skeptic
- leave-one-out range -0.32 to -0.12, sign flips 0; without severely affected donors -0.23 (p 0.365, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CNTFR in dopamine neurons.
case closed: nothing better to follow up.
receipt 13578: CNTFR in astrocytes, braak
- power
- full sample +0.02 (p 0.935, n 18), 95% CI -0.45 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.715, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.01 (p 0.969, n 18). could be the mix.
- skeptic
- leave-one-out range -0.13 to +0.16, sign flips 9; without severely affected donors +0.02 (p 0.935, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CNTFR in astrocytes.
case closed: nothing better to follow up.
Receipts
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