Description
The debate highlighted BBB penetration as a major hurdle for SPM therapeutics but provided no mechanistic understanding of transport barriers. This knowledge gap prevents rational design of CNS-penetrant pro-resolving mediators.
Source: Debate session sess_SDA-2026-04-01-gap-014 (Analysis: SDA-2026-04-01-gap-014)
Resolution criteria
Resolved when transport studies quantify BBB penetration kinetics for representative specialized pro-resolving mediators, including influx/efflux rates, transporter or metabolic barriers, and brain exposure at therapeutically relevant doses. Evidence must include in vitro BBB models plus in vivo brain/plasma pharmacokinetics, identify modifiable molecular determinants of CNS exposure, and update KG edges linking mediator structure, transport mechanism, and neuroinflammatory efficacy.