Pulmonary Arterial Hypertension and TGF-β Superfamily Signaling: Focus on Sotatercept.
Benjamin StumpAaron B WaxmanPublished in: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy (2024)
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.
Keyphrases
- pulmonary arterial hypertension
- transforming growth factor
- pulmonary artery
- pulmonary hypertension
- polycyclic aromatic hydrocarbons
- epithelial mesenchymal transition
- clinical trial
- cell proliferation
- electronic health record
- multiple sclerosis
- systematic review
- signaling pathway
- randomized controlled trial
- radiation therapy
- risk assessment
- squamous cell carcinoma
- mesenchymal stem cells
- genome wide identification
- lymph node
- human health