Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.45 from other evidence | 0.00 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 9 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress LAMTOR3 in a dopamine neuron, astrocyte and microglia tri-culture; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- 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 LAMTOR3 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- LAMTOR3 in dopamine neurons, braak+0.42 (p 0.265) → +0.28 (p 0.461)receipt 0416
Swarm cases
receipt 0416: LAMTOR3 in dopamine neurons, braak
- power
- full sample +0.28 (p 0.261, n 18), 95% CI -0.22 to +0.66. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.23 (p 0.355, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.33 (p 0.185, n 18). could be the mix.
- skeptic
- leave-one-out range +0.20 to +0.41, sign flips 0; without severely affected donors +0.28 (p 0.261, n 18). fragile.
- cell type
- strongest in oligodendrocytes: +0.70 (p 0.0013, n 18) vs +0.28 in dopamine neurons. proposing oligodendrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LAMTOR3 in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up LAMTOR3 · oligodendrocytes · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) +0.77 p 0.0059 (needs p < 0.0017)
Receipts
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