An emerging class of new therapeutics targeting TGF, Activin, and BMP ligands in pulmonary arterial hypertension.
Publication Date
2022-04-17Journal Title
Dev Dyn
ISSN
1058-8388
Publisher
Wiley
Language
en
Type
Article
This Version
AO
VoR
Metadata
Show full item recordCitation
Upton, P. D., Dunmore, B. J., Li, W., & Morrell, N. W. (2022). An emerging class of new therapeutics targeting TGF, Activin, and BMP ligands in pulmonary arterial hypertension.. Dev Dyn https://doi.org/10.1002/dvdy.478
Description
Funder: Department of Health; Id: http://dx.doi.org/10.13039/501100003921
Funder: Biomedical Research Center
Funder: NIHR; Id: http://dx.doi.org/10.13039/100006662
Abstract
Pulmonary arterial hypertension (PAH) is an often fatal condition, the primary pathology of which involves loss of pulmonary vascular perfusion due to progressive aberrant vessel remodeling. The reduced capacity of the pulmonary circulation places increasing strain on the right ventricle of the heart, leading to death by heart failure. Currently, licensed therapies are primarily vasodilators, which have increased the median post-diagnosis life expectancy from 2.8 to 7 years. Although this represents a substantial improvement, the search continues for transformative therapeutics that reverse established disease. The genetics of human PAH heavily implicates reduced endothelial bone morphogenetic protein (BMP) signaling as a causal role for the disease pathobiology. Recent approaches have focused on directly enhancing BMP signaling or removing the inhibitory influence of pathways that repress BMP signaling. In this critical commentary, we review the evidence underpinning the development of two approaches: BMP-based agonists and inhibition of activin/GDF signaling. We also address the key considerations and questions that remain regarding these approaches.
Keywords
CRITICAL COMMENTARY, CRITICAL COMMENTARIES
Sponsorship
British Heart Foundation (RG/19/3/34265)
British Heart Foundation (FS/SBSRF/20/31005)
National Institute for Health Research (IS-BRC-1215-20014)
Identifiers
dvdy478
External DOI: https://doi.org/10.1002/dvdy.478
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336505
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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