A relief for heart and lung - from nitroglycerin to innovative therapies
Prof. Dr. med. Ardeschir Ghofrani* (Spokesperson)
Dr. med. Reiner Frey
Prof. Dr. rer. nat. habil.
Johannes-Peter Stasch Bayer Pharma AG, Wuppertal
*Justus Liebig University Giessen
People who suffer from pulmonary hypertension are forced to accept that their quality of life is severely limited. Many patients die within a few years of diagnosis. Is there any way to stop this from happening?
Prof. Dr. Ardeschir Ghofrani, Dr. Reiner Frey and Prof. Dr. Johannes-Peter Stasch have developed an innovative drug that is effective in treating two forms of the serious and progressive disease. In the course of their work, the researchers discovered a mechanism of action that directly affects the molecular processes in the cardio-pulmonary system - and in the future could also be used to treat a number of other diseases. Johannes-Peter Stasch is an honorary professor for pharmaceutical research at the University of Halle-Wittenberg and was the senior fellow in cardiovascular research at Bayer Pharma AG. Reiner Frey also worked at Bayer as a senior fellow in clinical pharmacology. Ardeschir Ghofrani is head of the Pulmonary Hypertension Clinic at University Clinic Giessen und Marburg and is medical director of the Kerckhoff Clinic in Bad Nauheim.
The use of nitroglycerin in the treatment of cardiovascular diseases began 130 years ago. Initially used as an explosive, it is administered to treat angina pectoris. In the body, it releases nitric oxide (NO) that dilates blood vessels and lowers blood pressure, but it also degrades rapidly.
The body also produces NO. Patients with pulmonary hypertension do not produce enough NO and the pressure in the pulmonary arteries rises. Affected persons suffer from shortness of breath which makes everyday activities such as climbing stairs or walking longer distances difficult. Added to this are fatigue and circulatory problems that may result in fainting spells. Untreated, patients usually die of heart failure within a few years. To date, treatments to relieve pulmonary hypertension are available only for two types of the disease. Restoration of health can only be achieved for one form by means of an operation and the other form cannot be treated - a drug therapy has still not been found for the first type. Until now.
NO acts together with an enzyme that imparts its vasodilatory effect to the cells: "soluble guanylate cyclase" (sGC). Bayer researchers discovered a way to stimulate sGC independent of NO in 1994. Together with scientists from Giessen, they proved that this was an effective and promising way to treat pulmonary hypertension. Riociguat, the first active agent suitable to treat the disease, was synthesized for the first time in 2000. Thanks to its dual mechanism of action, Riociguat increases the effects of NO or replaces it to stimulate sGC to lower blood pressure in the lungs.
On the basis of this discovery, BAYER has developed the drug ADEMPAS® that is now approved in over 50 countries. It is effective in treating the symptoms of the disease and slows its progression. In the USA, it has been approved for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) - a form of the disease that has never before able to be treated by medication - if an operation is not possible or has been unsuccessful. The drug has also proven effective for certain types of pulmonary arterial hypertension (PAH). The drug was approved in the European Union in March 2014. Ongoing long-term studies have since documented that it is effective and safe over a period of up to two years. Other active agents from this class of substances are meanwhile being clinically tested for other diseases, e.g. in the treatment of chronic heart failure (cardiac insufficiency).
In addition to the great medical benefits, the drug also has vast commercial potential. Forecasts suggest annual turnover in excess of Euro 500m in the coming years. The development of the new drug for the treatment of pulmonary hypertension is exemplary of successful pharmaceutical innovation in Germany. The pharmacological principle was discovered in Germany. The active substance was developed and tested in Germany. The drug is produced in Germany. This has resulted in and will create numerous new jobs.
Schiller High School, Hameln, “Abitur” examination
1973 – 1978
Studies Leibniz University Hannover and Julius-Maximilians-University Würzburg Degree dissertation, Physical Chemistry Department, Julius-Maximilians- University, Würzburg
1978 – 1980
Alternative civilian service Neurochemistry Department, Würzburg University Hospital
1980 – 1983
Doctorate Dr. rer. nat., Neuropharmacology Department, Würzburg University Hospital, and Inorganic Chemistry Department, Bielefeld University,
Topic: Sila-piperidines and silylated piperidines with potential anti-Parkinson activity – syntheses, receptor binding studies and influences on the chemical signal transmission in the central nervous system”.