Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (830 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: entrectinib, taletrectinib, plx-7486 +10 | 1.00 |
| 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 | 10 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress NTRK3 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 NTRK3 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
- NTRK3 in oligodendrocytes, braak-0.22 (p 0.565) → +0.15 (p 0.705)receipt 3591
- NTRK3 in dopamine neurons, braak-0.49 (p 0.186) → -0.04 (p 0.909)receipt 3592
Swarm cases
receipt 3592: NTRK3 in dopamine neurons, braak
- power
- full sample -0.34 (p 0.167, n 18), 95% CI -0.70 to +0.15. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.35 (p 0.153, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.61 (p 0.0072, n 18). not the mix.
- skeptic
- leave-one-out range -0.44 to -0.25, sign flips 0; without severely affected donors -0.34 (p 0.167, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NTRK3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3591: NTRK3 in oligodendrocytes, braak
- power
- full sample -0.08 (p 0.767, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.07 (p 0.781, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.30 (p 0.232, n 18). could be the mix.
- skeptic
- leave-one-out range -0.17 to +0.04, sign flips 3; without severely affected donors -0.08 (p 0.767, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NTRK3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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