Advances in the discovery of drugs that treat pulmonary arterial hypertension

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Distal pulmonary arterial remodeling and elevated pulmonary vascular resistance are characteristic of pulmonary arterial hypertension (PAH). Current approved vasodilator-specific PAH therapy that includes phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids has demonstrated dramatic enhancement in functional capacity, quality of life, and invasive hemodynamics. However, none of these treatments are curative, underscoring the need to identify new pathophysiologic signaling pathways. Areas covered: The author provides a comprehensive review on current knowledge and recent development in the understanding of PAH. Furthermore, the author discusses PAH potential genetic causes as well as novel molecular signaling pathways. This article also reviews the currently approved PAH specific therapy based on pivotal clinical trials and ongoing clinical trials using novel compounds that specifically target PAH pathogenesis. Expert opinion: The discovery of novel signaling pathways–growth factors, tyrosine kinases, BMPs, estrogen, and serotonin–involved in the PAH pathobiology will lead within the next 5 years to the approval of new therapeutic agents targeting these different pathways. If proven beneficial, these new agents may reverse or at least prevent the progression of this devastating and lethal disease.

Original languageEnglish (US)
Pages (from-to)445-466
Number of pages22
JournalExpert Opinion on Drug Discovery
Volume18
Issue number4
DOIs
StatePublished - 2023

Keywords

  • BMPs
  • Combination therapy
  • Endothelin Receptor Antagonists
  • Nitric Oxide
  • PAH
  • Prostanoids
  • TGF ‐ β superfamily
  • estrogen
  • growth factors/tyrosinekinases
  • serotonin

ASJC Scopus subject areas

  • Drug Discovery

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