Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.39 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (1251 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: pesampator, farampator, becampanel +11 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 4 Parkinson's papers of 283 | 0.79 |
| pathways Reactome | 5 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress GRIA2 in oligodendrocytes; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position 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
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves LRRK2 kinase activity (pT73-Rab10) 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 GRIA2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; 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
- GRIA2 in oligodendrocytes, braak+0.45 (p 0.222) → +0.04 (p 0.912)receipt 0654
- GRIA2 in dopamine neurons, braak-0.23 (p 0.549) → +0.47 (p 0.204)receipt 0655
Swarm cases
receipt 0655: GRIA2 in dopamine neurons, braak
- power
- full sample +0.18 (p 0.471, n 18), 95% CI -0.31 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.15 (p 0.555, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.18 (p 0.482, n 18). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.33, sign flips 0; without severely affected donors +0.18 (p 0.471, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIA2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0654: GRIA2 in oligodendrocytes, braak
- power
- full sample +0.24 (p 0.332, n 18), 95% CI -0.25 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.24 (p 0.332, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.49 (p 0.041, n 18). not the mix.
- skeptic
- leave-one-out range +0.15 to +0.37, sign flips 0; without severely affected donors +0.24 (p 0.332, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIA2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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