"novel mechanisms targeted by drug trials in pulmonary arterial hypertension"

Chest. 2021 Oct 13:S0012-3692(21)04093-9. doi: 10.1016/j.chest.2021.10.010. Online ahead of print.ABSTRACTPulmonary arterial hypertension (PAH) is a rare disease associated with abnormally elevated pulmonary pressures and right heart failure resulting in high morbidity and mortality. While PAH prognosis has improved with the introduction of pulmonary vasodilators, disease progression remains a major problem. Given that available therapies are inadequate for preventing small vessel loss and obstruction, there is an active interest in identifying drugs capable of targeting angiogenesis and mechanisms involved in regulation of cell growth and fibrosis. Among the mechanisms linked to PAH pathogenesis, recent preclinical studies have identified promising compounds that are currently being tested in clinical trials. These drugs target seven of the major mechanisms associated with PAH pathogenesis: BMP signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. In this review, we will discuss the preclinical studies that led to prioritization of these mechanisms and will discuss recently completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells among others. We anticipate that the next generation of compounds will build upon the success of the current standard of care and improve clinical ou...
Source: Chest - Category: Respiratory Medicine Authors: Source Type: research