Pulmonary Arterial Hypertension and TGF-β Superfamily Signaling: Focus on Sotatercept

Overview

Journal BioDrugs

Specialties Allergy & Immunology
Genetics
Pharmacology

Date 2024 Sep 18

PMID 39292393

Authors

Benjamin Stump

Aaron B Waxman

Affiliations

Soon will be listed here.

Abstract

Pulmonary arterial hypertension (PAH) is a rare and progressive disease that continues to remain highly morbid despite multiple advances in medical therapies. There remains a persistent and desperate need to identify novel methods of treating and, ideally, reversing the pathologic vasculopathy that results in PAH development and progression. Sotatercept is a first-in-class fusion protein that is believed to primarily inhibit activin signaling resulting in decreased cell proliferation and differentiation, though the exact mechanism remains uncertain. Here, we review the currently available PAH therapies, data highlighting the importance of transforming growth factor-β (TGF-β) superfamily signaling in the development of PAH, and the published and on-going clinical trials evaluating sotatercept in the treatment of PAH. We will also discuss preclinical data supporting the potential use of the fusion protein KER-012 in the inhibition of aberrant TGF-β superfamily signaling to ameliorate the obstructive vasculopathy of PAH.

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