Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.07 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (2373 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: lestaurtinib, larotrectinib sulfate, cep-2563 +10 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 7 Parkinson's papers of 840 | 0.73 |
| pathways Reactome | 14 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress NTRK2 in astrocytes; measure phospho-ERK and phospho-AKT response to GDNF 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; existing compounds already reach the inhibition arm.
- Molecular readout
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- 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 NTRK2 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; 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
- NTRK2 in astrocytes, braak-0.46 (p 0.217) → +0.26 (p 0.504)receipt 3817
- NTRK2 in dopamine neurons, braak+0.09 (p 0.825) → -0.22 (p 0.569)receipt 3818
Swarm cases
receipt 3818: NTRK2 in dopamine neurons, braak
- power
- full sample -0.01 (p 0.962, n 18), 95% CI -0.48 to +0.46. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.09 (p 0.735, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.09 (p 0.735, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.09, sign flips 7; without severely affected donors -0.01 (p 0.962, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NTRK2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3817: NTRK2 in astrocytes, braak
- power
- full sample -0.16 (p 0.515, n 18), 95% CI -0.59 to +0.33. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.21 (p 0.398, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.13 (p 0.621, n 18). could be the mix.
- skeptic
- leave-one-out range -0.31 to -0.07, sign flips 0; without severely affected donors -0.16 (p 0.515, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NTRK2 in astrocytes.
case closed: nothing better to follow up.
Receipts
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