Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched, including oligodendrocytes; strongest in choroid plexus epithelial cells | 0.75 |
| chemistry Open Targets | compounds already reach it: ziritaxestat | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 281 | 0.91 |
| pathways Reactome | 1 pathway; mostly energy | 0.60 |
Knock down and overexpress ENPP2 in oligodendrocytes; measure oxygen consumption rate and ATP output 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
- oxygen consumption rate and ATP output
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves oxygen consumption rate 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 ENPP2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; 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
- ENPP2 in dopamine neurons, braak+0.25 (p 0.517) → +0.49 (p 0.183)receipt 12497
- ENPP2 in oligodendrocytes, braak+0.55 (p 0.125) → +0.09 (p 0.815)receipt 12496
Swarm cases
receipt 12497: ENPP2 in dopamine neurons, braak
- power
- full sample +0.29 (p 0.235, n 18), 95% CI -0.20 to +0.67. 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
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.48 (p 0.046, n 18). not the mix.
- skeptic
- leave-one-out range +0.20 to +0.44, sign flips 0; without severely affected donors +0.29 (p 0.235, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ENPP2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 12496: ENPP2 in oligodendrocytes, braak
- power
- full sample +0.31 (p 0.214, n 18), 95% CI -0.19 to +0.68. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.21 (p 0.398, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.20 (p 0.424, n 18). could be the mix.
- skeptic
- leave-one-out range +0.22 to +0.49, 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 ENPP2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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