Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.04 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (20 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: acitretin, mofarotene, irx-4204 +3 | 1.00 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 9 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress RXRB 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.
- 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 RXRB 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
- RXRB in oligodendrocytes, braak-0.35 (p 0.361) → -0.37 (p 0.331)receipt 6193
- RXRB in dopamine neurons, braak+0.17 (p 0.671) → -0.01 (p 0.982)receipt 6194
Swarm cases
receipt 6194: RXRB in dopamine neurons, braak
- power
- full sample +0.07 (p 0.774, n 18), 95% CI -0.41 to +0.52. 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
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.03 (p 0.894, n 18). could be the mix.
- skeptic
- leave-one-out range -0.04 to +0.20, sign flips 5; without severely affected donors +0.07 (p 0.774, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RXRB in dopamine neurons.
case closed: nothing better to follow up.
receipt 6193: RXRB in oligodendrocytes, braak
- power
- full sample -0.39 (p 0.105, n 18), 95% CI -0.73 to +0.09. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.41 (p 0.091, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.39 (p 0.107, n 18). could be the mix.
- skeptic
- leave-one-out range -0.51 to -0.31, sign flips 0; without severely affected donors -0.39 (p 0.105, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RXRB in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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