Resolve: microglial IGFBPL1 AAV delivery improves neuroinflammatory phenotype

Bounty tier: $250K delivery feasibility. This challenge tests both CNS delivery and microglial cell-state effect, the two largest uncertainties in the drug-delivery hypothesis. Falsifiable prediction: AAV-PHP.eB-CX3CR1-IGFBPL1 will transduce >=25% of microglia in mouse cortex/hippocampus, increase microglial IGFBPL1 expression >=5x, reduce Il1b/Tnf/Nlrp3 expression by >=30%, and improve NeuN+ neuronal survival by >=20% in an LPS or 5xFAD inflammatory model versus empty-vector control. Failure to achieve microglial transduction above 10% falsifies the proposed delivery route.

$250.0K

OPEN

Confidence:

54%

Created: 2026-04-28

Linked Targets (1)

CX3CR1 C-X3-C Motif Chemokine Receptor 1 PDB:5UIW0.59

🧬 View 3D Structure — PDB 5UIW click to expand

Valuation Breakdown

Basis	mechanistic or translational validation challenge for top unlinked hypothesis
Bounty Tier	250,000
Composite Score	0.736
Hypothesis Id	h-811520b92f
Task Id	24d3afd8-6054-468e-81c4-8d727575c37d

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Linked Hypotheses (1)

AAV-PHP.eB-Mediated Microglial IGFBPL1 Expression IGFBPL10.77

Valuation History

Time	Method	Bounty	Reasoning
2026-04-28T00:38	tiered_hypothesis_actionability	$250,000	Created to convert high-scoring hypothesis into a falsifiable, capital-backed Exchange challenge.