Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.04 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in pancreatic islet cells | 0.75 |
| chemistry Open Targets | compounds already reach it: tolbutamide, glipizide, glimepiride +9 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 1,024 | 0.91 |
| pathways Reactome | 3 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress ABCC8 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; existing compounds already reach the inhibition arm.
- 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 ABCC8 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
- ABCC8 in dopamine neurons, braak-0.73 (p 0.026) → +0.06 (p 0.870)receipt 5817
- ABCC8 in oligodendrocytes, braak+0.15 (p 0.697) → -0.11 (p 0.773)receipt 5816
Swarm cases
receipt 5817: ABCC8 in dopamine neurons, braak
- power
- full sample -0.28 (p 0.265, n 18), 95% CI -0.66 to +0.22. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.29 (p 0.239, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.39 (p 0.109, n 18). could be the mix.
- skeptic
- leave-one-out range -0.43 to -0.19, sign flips 0; without severely affected donors -0.28 (p 0.265, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ABCC8 in dopamine neurons.
case closed: nothing better to follow up.
receipt 5816: ABCC8 in oligodendrocytes, braak
- power
- full sample +0.04 (p 0.881, n 18), 95% CI -0.44 to +0.50. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.04 (p 0.881, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.11 (p 0.671, n 18). could be the mix.
- skeptic
- leave-one-out range -0.08 to +0.16, sign flips 5; without severely affected donors +0.04 (p 0.881, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ABCC8 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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