Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (856 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: bms-986020 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 383 | 0.91 |
| pathways Reactome | 3 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress LPAR1 in oligodendrocytes; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux 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
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) activity 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 LPAR1 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; 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
- LPAR1 in oligodendrocytes, braak-0.11 (p 0.777) → +0.55 (p 0.128)receipt 8698
- LPAR1 in dopamine neurons, braak-0.03 (p 0.946) → +0.35 (p 0.362)receipt 8699
Swarm cases
receipt 8699: LPAR1 in dopamine neurons, braak
- power
- full sample +0.19 (p 0.450, n 18), 95% CI -0.30 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.17 (p 0.504, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.16 (p 0.515, n 18). could be the mix.
- skeptic
- leave-one-out range +0.09 to +0.33, sign flips 0; without severely affected donors +0.19 (p 0.450, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LPAR1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 8698: LPAR1 in oligodendrocytes, braak
- power
- full sample +0.30 (p 0.228, n 18), 95% CI -0.20 to +0.67. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.30 (p 0.232, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.31 (p 0.218, n 18). could be the mix.
- skeptic
- leave-one-out range +0.21 to +0.46, sign flips 0; without severely affected donors +0.30 (p 0.228, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LPAR1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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