Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in bergmann glia | 0.75 |
| chemistry Open Targets | compounds already reach it: gsk-690693, cep-2563, ucn-01 +3 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 526 | 0.82 |
| pathways Reactome | 20 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress PRKCA 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 PRKCA 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
- PRKCA in dopamine neurons, braak-0.74 (p 0.021) → -0.09 (p 0.820)receipt 7915
- PRKCA in oligodendrocytes, braak+0.01 (p 0.982) → -0.74 (p 0.023)receipt 7914
Swarm cases
receipt 7915: PRKCA in dopamine neurons, braak
- power
- full sample -0.31 (p 0.214, n 18), 95% CI -0.68 to +0.19. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.38 (p 0.120, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.44 (p 0.070, n 18). could be the mix.
- skeptic
- leave-one-out range -0.48 to -0.22, sign flips 0; without severely affected donors -0.31 (p 0.214, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PRKCA in dopamine neurons.
case closed: nothing better to follow up.
receipt 7914: PRKCA in oligodendrocytes, braak
- power
- full sample -0.35 (p 0.153, n 18), 95% CI -0.70 to +0.14. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.35 (p 0.159, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.40 (p 0.099, n 18). could be the mix.
- skeptic
- leave-one-out range -0.51 to -0.27, sign flips 0; without severely affected donors -0.35 (p 0.153, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PRKCA in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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