Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.05 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched, including oligodendrocytes; strongest in bergmann glia | 0.75 |
| chemistry Open Targets | compounds already reach it: ly404039, pomaglumetad methionil anhydrous, decoglurant | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 207 | 0.82 |
| pathways Reactome | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress GRM3 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 GRM3 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
- GRM3 in dopamine neurons, braak+0.48 (p 0.186) → +0.28 (p 0.464)receipt 5494
- GRM3 in oligodendrocytes, braak+0.35 (p 0.355) → -0.04 (p 0.912)receipt 5493
Swarm cases
receipt 5494: GRM3 in dopamine neurons, braak
- power
- full sample +0.36 (p 0.148, n 18), 95% CI -0.13 to +0.71. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.41 (p 0.089, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.47 (p 0.047, n 18). not the mix.
- skeptic
- leave-one-out range +0.27 to +0.53, sign flips 0; without severely affected donors +0.36 (p 0.148, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRM3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 5493: GRM3 in oligodendrocytes, braak
- power
- full sample +0.25 (p 0.315, n 18), 95% CI -0.24 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.25 (p 0.315, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.23 (p 0.365, n 18). could be the mix.
- skeptic
- leave-one-out range +0.17 to +0.40, sign flips 0; without severely affected donors +0.25 (p 0.315, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRM3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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