Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.06 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including brain excitatory neurons; strongest in t-cells | 0.75 |
| 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 | 2 Parkinson's papers of 218 | 0.85 |
| pathways Reactome | 6 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress CAMK4 in dopamine neurons; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) 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.
- Molecular readout
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- 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 PINK1–parkin mitophagy flux (mt-Keima) 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 CAMK4 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); 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
- CAMK4 in dopamine neurons, braak+0.42 (p 0.255) → +0.75 (p 0.020)receipt 4188
Swarm cases
receipt 4188: CAMK4 in dopamine neurons, braak
- power
- full sample +0.61 (p 0.0077, n 18), 95% CI +0.19 to +0.84. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.59 (p 0.0099, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.61 (p 0.0077, n 18). not the mix.
- skeptic
- leave-one-out range +0.57 to +0.81, sign flips 0; without severely affected donors +0.61 (p 0.0077, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CAMK4 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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