Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | enriched in the midbrain (37 nTPM), where the nigral dopamine neurons sit | 0.90 |
| chemistry Open Targets | a small-molecule pocket: indatuximab ravtansine | 0.60 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 19 pathways; mostly protein handling | 0.90 |
Knock down and overexpress SDC1 in dopamine neurons; measure proteasome activity and the load of ubiquitinated protein and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- Rule-out
- If neither arm moves proteasome 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 SDC1 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- SDC1 in dopamine neurons, braak+0.27 (p 0.478) → -0.79 (p 0.011)receipt 10107
Swarm cases
receipt 10107: SDC1 in dopamine neurons, braak
- power
- full sample -0.28 (p 0.261, n 18), 95% CI -0.66 to +0.22. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.29 (p 0.246, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.40 (p 0.101, n 18). could be the mix.
- skeptic
- leave-one-out range -0.41 to -0.19, sign flips 0; without severely affected donors -0.28 (p 0.261, n 18). fragile.
- cell type
- strongest in oligodendrocytes: -0.60 (p 0.0080, n 18) vs -0.28 in dopamine neurons. proposing oligodendrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SDC1 in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up SDC1 · oligodendrocytes · braak: substantia nigra, an independent cohort: not measured
Receipts
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