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 oligodendrocytes; strongest in choroid plexus epithelial cells | 0.75 |
| chemistry Open Targets | compounds already reach it: rogaratinib, hmpl-453, nintedanib esylate +24 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 4,379 | 0.82 |
| pathways Reactome | 18 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress FGFR2 in oligodendrocytes; measure phospho-ERK and phospho-AKT response to GDNF and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves phospho-ERK 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 FGFR2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- FGFR2 in dopamine neurons, braak+0.84 (p 0.005) → -0.49 (p 0.181)receipt 6661
- FGFR2 in oligodendrocytes, braak-0.02 (p 0.962) → -0.52 (p 0.155)receipt 6660
Swarm cases
receipt 6661: FGFR2 in dopamine neurons, braak
- power
- full sample -0.02 (p 0.935, n 18), 95% CI -0.48 to +0.45. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.03 (p 0.894, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.12 (p 0.627, n 18). could be the mix.
- skeptic
- leave-one-out range -0.15 to +0.12, sign flips 6; 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 FGFR2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 6660: FGFR2 in oligodendrocytes, braak
- power
- full sample +0.03 (p 0.901, n 18), 95% CI -0.44 to +0.49. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.01 (p 0.969, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.02 (p 0.935, n 18). could be the mix.
- skeptic
- leave-one-out range -0.06 to +0.19, sign flips 7; without severely affected donors +0.03 (p 0.901, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FGFR2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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