Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (339 nCPM) | 1.00 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 562 | 0.82 |
| pathways Reactome | 1 pathway; mostly energy | 0.60 |
Knock down and overexpress ASPA 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.
- 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 ASPA 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
- ASPA in dopamine neurons, braak-0.57 (p 0.109) → +0.11 (p 0.778)receipt 3217
- ASPA in oligodendrocytes, braak+0.60 (p 0.090) → +0.52 (p 0.149)receipt 3216
Swarm cases
receipt 3217: ASPA in dopamine neurons, braak
- power
- full sample +0.03 (p 0.922, n 18), 95% CI -0.45 to +0.49. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.05 (p 0.847, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.09 (p 0.715, n 18). could be the mix.
- skeptic
- leave-one-out range -0.09 to +0.13, sign flips 5; without severely affected donors +0.03 (p 0.922, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ASPA in dopamine neurons.
case closed: nothing better to follow up.
receipt 3216: ASPA in oligodendrocytes, braak
- power
- full sample +0.26 (p 0.294, n 18), 95% CI -0.23 to +0.65. 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: +0.12 (p 0.640, n 18). could be the mix.
- skeptic
- leave-one-out range +0.15 to +0.41, sign flips 0; without severely affected donors +0.26 (p 0.294, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ASPA in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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