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Sotatercept reduces bone morphogenetic protein signaling in patients with pulmonary arterial hypertension.
Science Translational Medicine · · Journal Article
Jones, De Bie + more
Abstract ↗AI summary
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In peripheral blood from pulmonary arterial hypertension patients, sotatercept treatment in a pilot of nine patients is linked to reduced BMP pathway signaling, not increased BMPR-II activity.
- Why it matters: Target engagement biomarkers are needed in PAH because lung tissue is inaccessible for molecular profiling, despite TGF-β/BMP pathway imbalance having causal roles.
- What they did: Using StratosPHere 1 samples, the study measured BMPR-II receptor levels and downstream BMP signaling in whole blood, then built a repeatable, longitudinally stable transcriptomic biomarker panel.
- The result: The biomarker panel showed BMP pathway transcriptomic signatures associated with clinical outcomes and mortality, and in nine sotatercept-treated patients suggested reduced signaling, possibly via depletion of circulating BMP9 and BMP10.
The findingWhy it mattersWhat they didThe result
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