Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.27 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in prostatic glandular cells | 0.75 |
| chemistry Open Targets | a small-molecule pocket: dibotermin alfa, eptotermin alfa | 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 | 1 pathway; mostly growth signalling | 0.60 |
Knock down and overexpress BMPR1B in astrocytes; measure phospho-ERK and phospho-AKT response to GDNF and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves phospho-ERK 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 BMPR1B in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- BMPR1B in astrocytes, braak-0.20 (p 0.602) → +0.05 (p 0.893)receipt 1518
- BMPR1B in dopamine neurons, braak+0.46 (p 0.209) → +0.17 (p 0.671)receipt 1519
Swarm cases
receipt 1519: BMPR1B in dopamine neurons, braak
- power
- full sample +0.34 (p 0.173, n 18), 95% CI -0.16 to +0.69. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.35 (p 0.153, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.41 (p 0.087, n 18). could be the mix.
- skeptic
- leave-one-out range +0.24 to +0.46, sign flips 0; without severely affected donors +0.34 (p 0.173, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for BMPR1B in dopamine neurons.
case closed: nothing better to follow up.
receipt 1518: BMPR1B in astrocytes, braak
- power
- full sample -0.06 (p 0.800, n 18), 95% CI -0.52 to +0.42. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.935, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.08 (p 0.761, n 18). could be the mix.
- skeptic
- leave-one-out range -0.17 to +0.08, sign flips 4; without severely affected donors -0.06 (p 0.800, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for BMPR1B in astrocytes.
case closed: nothing better to follow up.
Receipts
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