Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.74 (overall 0.48) | 0.74 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | compounds already reach it: glembatumumab vedotin | 0.81 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 75 Parkinson's papers of 825 | 0.43 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress GPNMB in a dopamine neuron, astrocyte and microglia tri-culture; measure a transcriptome-wide state shift (bulk RNA-seq) 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; existing compounds already reach the inhibition arm.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 GPNMB in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.61; 2026-10-26 0.61; 2026-10-16 0.61.
Sealed predictions
- GPNMB in microglia, braak-0.44 (p 0.240) → +0.25 (p 0.514)receipt 10870
- GPNMB in dopamine neurons, braak-0.36 (p 0.336) → +0.18 (p 0.652)receipt 0270
In the sealed studies
- The lysosomal axis in dopamine neurons: did not hold
- An antigen-presenting microglial response: did not hold
Swarm cases
receipt 0270: GPNMB in dopamine neurons, braak
- power
- full sample +0.01 (p 0.956, n 18), 95% CI -0.46 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.01 (p 0.956, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.04 (p 0.874, n 18). could be the mix.
- skeptic
- leave-one-out range -0.13 to +0.11, sign flips 7; without severely affected donors +0.01 (p 0.956, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GPNMB in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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