Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.10 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (142 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: enflurane, isoflurane, methoxyflurane +3 | 1.00 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 1 stopped | 0.20 |
| literature PubMed | 2 Parkinson's papers of 104 | 0.85 |
| pathways Reactome | 1 pathway; mostly dopamine synapse | 1.00 |
Knock down and overexpress GLRB in oligodendrocytes; measure evoked dopamine release and dopamine transporter uptake 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
- evoked dopamine release and dopamine transporter uptake
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves evoked dopamine release 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 GLRB in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; 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
- GLRB in dopamine neurons, braak+0.22 (p 0.565) → +0.32 (p 0.400)receipt 2560
- GLRB in oligodendrocytes, braak-0.14 (p 0.714) → +0.04 (p 0.928)receipt 2559
Swarm cases
receipt 2560: GLRB in dopamine neurons, braak
- power
- full sample +0.27 (p 0.277, n 18), 95% CI -0.22 to +0.65. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.36 (p 0.148, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.36 (p 0.148, n 18). could be the mix.
- skeptic
- leave-one-out range +0.17 to +0.43, sign flips 0; without severely affected donors +0.27 (p 0.277, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GLRB in dopamine neurons.
case closed: nothing better to follow up.
receipt 2559: GLRB in oligodendrocytes, braak
- power
- full sample -0.10 (p 0.702, n 18), 95% CI -0.54 to +0.39. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.28 (p 0.265, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.24 (p 0.328, n 18). could be the mix.
- skeptic
- leave-one-out range -0.23 to +0.03, sign flips 2; without severely affected donors -0.10 (p 0.702, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GLRB in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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