Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.53 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in thymocytes | 0.75 |
| chemistry Open Targets | compounds already reach it: prilocaine, quinidine gluconate, tetracaine +70 | 1.00 |
| trials ClinicalTrials.gov | 3 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | 6 Parkinson's papers of 173 | 0.74 |
| pathways Reactome | 3 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress SCN3A 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 SCN3A 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.
Earlier readings: 2026-10-26 0.61; 2026-10-25 0.61; 2026-10-24 0.61; 2026-10-23 0.61.
Sealed predictions
- SCN3A in oligodendrocytes, braak-0.10 (p 0.807) → +0.50 (p 0.172)receipt 0613
- SCN3A in dopamine neurons, braak+0.74 (p 0.022) → +0.34 (p 0.373)receipt 0185
Swarm cases
receipt 0613: SCN3A in oligodendrocytes, braak
- power
- full sample +0.05 (p 0.854, n 18), 95% CI -0.43 to +0.50. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.05 (p 0.854, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.09 (p 0.722, n 18). could be the mix.
- skeptic
- leave-one-out range -0.07 to +0.19, sign flips 4; without severely affected donors +0.05 (p 0.854, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SCN3A in oligodendrocytes.
case closed: nothing better to follow up.
receipt 0185: SCN3A in dopamine neurons, braak
- power
- full sample +0.58 (p 0.012, n 18), 95% CI +0.15 to +0.82. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.54 (p 0.021, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.50 (p 0.033, n 18). not the mix.
- skeptic
- leave-one-out range +0.52 to +0.72, sign flips 0; without severely affected donors +0.58 (p 0.012, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SCN3A in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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