Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (307 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: patritumab deruxtecan, av-203, duligotuzumab +14 | 1.00 |
| trials ClinicalTrials.gov | 4 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | 5 Parkinson's papers of 2,663 | 0.76 |
| pathways Reactome | 15 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress ERBB3 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 ERBB3 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
- ERBB3 in dopamine neurons, braak-0.09 (p 0.815) → -0.56 (p 0.117)receipt 11615
- ERBB3 in oligodendrocytes, braak+0.14 (p 0.725) → -0.74 (p 0.024)receipt 11614
Swarm cases
receipt 11615: ERBB3 in dopamine neurons, braak
- power
- full sample -0.22 (p 0.389, n 18), 95% CI -0.62 to +0.28. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.26 (p 0.298, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.32 (p 0.201, n 18). could be the mix.
- skeptic
- leave-one-out range -0.35 to -0.10, sign flips 0; without severely affected donors -0.22 (p 0.389, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ERBB3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11614: ERBB3 in oligodendrocytes, braak
- power
- full sample -0.08 (p 0.748, n 18), 95% CI -0.53 to +0.40. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.07 (p 0.774, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.14 (p 0.567, n 18). could be the mix.
- skeptic
- leave-one-out range -0.20 to +0.05, sign flips 2; without severely affected donors -0.08 (p 0.748, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ERBB3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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