TRPV4 antagonist efficacy in a post-hemorrhagic hydrocephalus pig model

Orally bioavailable TRPV4 antagonist GSK2789917 prevents progression to severe post-hemorrhagic hydrocephalus in a pig model when given 2 days after intraventricular hemorrhage.

• Why it matters: Effective non-surgical treatments for PHH are lacking, partly because few gyrencephalic animal models reproduce human-like disease features.
• What they did: The study created a swine IVH model recapitulating severe PHH traits, then administered GSK2789917 to test whether TRPV4 inhibition alters ventriculomegaly, intracranial pressure, and neuroinflammation.
• The result: GSK2789917 penetrates the blood-brain barrier, prevents ventriculomegaly, suppresses early ICP elevations, and prevents or reverses inflammasome activation.

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