Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in salivary acinar cells | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | 8 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | 4 Parkinson's papers of 6,085 | 0.79 |
| pathways Reactome | 17 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress BLM 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.
- 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 BLM 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
- BLM in dopamine neurons, braak+0.40 (p 0.288) → -0.44 (p 0.240)receipt 13943
- BLM in oligodendrocytes, braak-0.46 (p 0.209) → -0.16 (p 0.682)receipt 13942
Swarm cases
receipt 13943: BLM in dopamine neurons, braak
- power
- full sample +0.02 (p 0.949, n 18), 95% CI -0.45 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.949, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.03 (p 0.915, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.12, sign flips 6; without severely affected donors +0.02 (p 0.949, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for BLM in dopamine neurons.
case closed: nothing better to follow up.
receipt 13942: BLM in oligodendrocytes, braak
- power
- full sample -0.21 (p 0.398, n 18), 95% CI -0.62 to +0.28. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.16 (p 0.532, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.03 (p 0.901, n 18). could be the mix.
- skeptic
- leave-one-out range -0.36 to -0.12, sign flips 0; without severely affected donors -0.21 (p 0.398, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for BLM in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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