New therapies for pulmonary arterial hypertension: an update on current bench to bedside translation

Laurence Dewachter, CĂ©line Dewachter, Robert Naeije
Expert Opinion on Investigational Drugs 2010, 19 (4): 469-88

IMPORTANCE OF THE FIELD: Treatments of pulmonary arterial hypertension (PAH) that have so far proven efficacious are all based on the restoration of endothelium control of pulmonary vascular tone and structure, by administration of prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. However, results remain unsatisfactory, with persistent high mortality, insufficient clinical improvement and no convincing report of any reversal of the disease process.

AREAS COVERED IN THIS REVIEW: New antiproliferative approaches that aim to actively limit pulmonary vascular remodeling are being sought. Several such treatments have shown promise in experimental models and in preliminary clinical studies. Noteworthy among these are dichloroacetate, survivin antagonists, nuclear factor of activated T-cell inhibitors, PPAR-gamma agonists, tyrosine kinase inhibitors, Rho-kinase inhibitors, statins, vasoactive intestinal peptide, soluble guanylate cyclase stimulators/activators, adrenomedullin, elastase inhibitors, serotonin reuptake inhibitors, anti-inflammatory agents, and bone marrow-derived progenitor cells.

WHAT THE READER WILL GAIN: Update on various strategies targeting proliferative, inflammatory and regenerating processes currently under evaluation in patients with PAH.

TAKE HOME MESSAGE: In spite of favorable results in experimental models, none of these strategies has achieved the ultimate goal of curing PAH. Further developments will depend on progress made in our pathobiological understanding of the disease and carefully designed randomized, controlled trials.

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