Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.07 (overall 0.04) | 0.07 |
| cell type Human Protein Atlas | group enriched in brain excitatory neurons (29 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 529 | 0.85 |
| pathways Reactome | 31 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress FGF5 in dopamine neurons; measure phospho-ERK and phospho-AKT response to GDNF and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- 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 FGF5 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- FGF5 in dopamine neurons, braak+0.22 (p 0.569) → +0.45 (p 0.219)receipt 5744
Swarm cases
receipt 5744: FGF5 in dopamine neurons, braak
- power
- full sample +0.30 (p 0.225, n 18), 95% CI -0.19 to +0.67. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.29 (p 0.235, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.33 (p 0.185, n 18). could be the mix.
- skeptic
- leave-one-out range +0.20 to +0.43, sign flips 0; without severely affected donors +0.30 (p 0.225, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FGF5 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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