“The Solvay Pharmaceuticals Conferences: where industry meets academia in a search for novel therapies”

Pulmonary Arterial Hypertension: New Insights

Pulmonary arterial hypertension is diagnosed if the mean pulmonary artery pressure is greater than 25 mmHg at rest or at least 30 mmHg during exercise and is associated with enhanced pulmonary vascular resistance and with a mean pulmonary wedge pressure and left ventricular end diastolic pressure of less than 15 mmHg [1]. Persistent elevation of pulmonary artery pressure and vascular resistance leads to right ventricular failure and death [1]. The pathogenesis of pulmonary arterial hypertension involves several contributing processes: vasoconstriction, smooth muscle and endothelial cell proliferation, and thrombosis.

Calcium channel blockers, anticoagulants, prostacyclin and its analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors dominate therapy of pulmonary arterial hypertension today. However, this therapy does not improve long-term survival and the right heart dysfunction remains the main cause of death of pulmonary arterial hypertension sufferers, despite the implemented therapy.

Disease modification and preventive strategies must be better addressed in order to achieve tangible therapeutic benefits for patients who are at risk for developing or already have pulmonary arterial hypertension. Therefore, the focus of therapy is shifting from treatment of the acutely sick towards disease modifying measures and health management. Such fundamental changes can only be achieved if interest of pharmaceutical industry is shifted towards research in this field.

During the last decade progress in understanding of the role of endothelin receptors in vasoconstriction and proliferation was made, knowledge of mechanisms controlling circulation in the pulmonary artery has expanded, understanding of nitric oxide in the pathogenesis of pulmonary arterial hypertension has matured and new medicines such as bosentan, a dual endothelin A and B receptor antagonist [2], and sildenafil, a phosphodiesterase type 5 inhibitor, have been introduced [3].

The emerging therapies of pulmonary arterial hypertension involve 5-hydroxytryptamine transporter blockers, vasoactive intestinal peptide, statins, and voltage-gated potassium channel modulators [1].

The challenge is to ensure that new findings related to the pathogenesis of pulmonary arterial hypertension are adequately translated into therapies and are driving progress of drug finding by means of systems biology approaches combined with intelligent synthesis of molecules [4]. Increasing understanding of processes responsible for restriction of pulmonary circulation and vascular remodeling provides new basis for modification of the disease early in its course with the aim of improving quality of life of patients marked by significant prolongation of survival.

The current volume contains contributions from the Tenth Solvay Pharmaceuticals Conference on Pulmonary Arterial Hypertension held in Riga (Latvia) December 11–12, 2008.

It has been the aim of these conferences to bring together scientists from academia and from industry in order to stimulate exchange between them in a challenging setting. The focus of the recent conference was placed on the cardiopulmonary disorder “pulmonary artery hypertension”, characterized by multiple unknown aspects which obscure understanding of mechanisms involved in its pathogenesis, ways of its prevention and means limiting its progress, and on the aspects of drug finding and development. New diagnostic procedures and insights into therapy were highlighted including imaging, novel functional diagnostic approaches, disease monitoring, biomarkers and future therapeutics.

W. Cautreels, C. Steinborn, L. Turski

References

[1] A. Puri, M.D. McGoon, S.S. Kushwaha. Pulmonary arterial hypertension: current therapeutic strategies. Nat. Clin. Pract. Cardiovasc. Med. 4 (2007) 319–329.

[2] L.J. Rubin, D.B. Badesch, R.J. Barst et al. Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med. 346 (2002) 896–903.

[3] S. Prasad, J. Wilkinson, M.A. Gatzoulis. Sildenafil in primary pulmonary hypertension. N. Engl. J. Med. 343 (2000) 1342.

[4] L. Turski. New business models required for today's drug development. Conceptuur 44 (2005) 6–7.

As of February 2010, Solvay Pharmaceuticals is part of Abbott.