Prestigious Lefoulon-Delalande Foundation Prize awarded to Professor Dario DiFrancesco for the discovery of the If pacemaker current and its therapeutic application

Paris, June 11, 2008: Professor Dario DiFrancesco today received the prestigious Lefoulon-Delalande Foundation Prize for the discovery of the If current in the sinus node, which is the physiological "pacemaker" of the heart. Professor DiFrancesco demonstrated that the If current is a key determinant for the generation and control of heart rate. This discovery led to several clinically-relevant applications, including the development of Procoralan®* (ivabradine), the first selective and specific If inhibitor, which provides pure heart rate reduction and has already gained a favored place in the therapeutic armamentarium.

The Lefoulon-Delalande Foundation/Institut de France Prize

Created in 2002, the Lefoulon-Delalande Foundation Prize is awarded each year to a scientist who has made important contributions to cardiovascular physiology, biology, or medicine. Based on the suggestion of an international scientific panel, chaired by Professor Alain Carpentier, the Institut de France has decided to grant the “Grand Prix Scientifique” 2008 to Dario DiFrancesco, Director of the Laboratory of Molecular Physiology and Neurobiology - University of Milan, Italy. The prize, which is recognized internationally as the most prestigious in the cardiovascular field, is awarded for Professor DiFrancesco’s discovery of the cellular mechanism underlying the generation and regulation of heart rate, and the therapeutic application of this discovery.


The fundamental discovery of the pacemaker I_f current

The heart beats rhythmically thanks to the existence of a special "engine": the sinus node, called "the natural pacemaker". The cells of the sinus node are able to generate a spontaneous regular action potential and thereby modulate heart rate.

In the late 1970s, Dario DiFrancesco started to study the cellular mechanisms governing the generation of this spontaneous electrical activity in the sinus node. This led to the discovery of a major ionic current that is responsible for the generation of spontaneous activity, the I_f current. In a paper published in Nature in 1979 along with Hilary Brown and Susan Noble (Brown, DiFrancesco & Noble, 1979), DiFrancesco and collaborators described for the first time this I_f current, the “f” standing for “funny”. It was called "funny" because it had very unusual properties when compared to other cardiac currents known at the time. It is since considered as one of the most important ionic currents for the generation and control of heart rate.

It is established that heart rate is a key determinant of cardiac ischemia. In the last decade, growing evidence has emerged from large-scale epidemiological studies that elevated heart rate is associated with an increased risk of cardiovascular events. This association has been reported in apparently healthy individuals and in patients across the cardiovascular disease spectrum. The relevance of the I_f current in the generation of heart rate and its control made it an ideal target to develop new drugs aiming at selectively reducing heart rate.


From a fundamental discovery to a therapeutic innovation

The search for selective and specific inhibition of the I_f current led to Servier Research’s discovery of Procoralan (ivabradine). Procoralan is such an innovation that a group of experts has awarded Servier the prestigious Prix Galien 2008 in France for a medicinal product used in outpatient treatment. Procoralan slows the heart rate, while at the same time preserving other parameters of cardiac function, notably contraction strength. This mode of action confers on Procoralan properties that are particularly useful in coronary patients. Procoralan has powerful anti-ischemic efficacy, greatly reduces the number of angina attacks, and increases exercise capacity, thus enabling patients to resume their usual activities without suffering pain. Procoralan is currently available in 45 countries in Europe and other parts of the world. The prevention benefits of Procoralan are currently being evaluated in the landmark BEAUTIFUL study whose results will be presented at the European Society of Cardiology (ESC) congress in September in Munich, Germany.


*Depending on the country, ivabradine is available as Procoralan®, Coralan®, Coraxan®, or Corlentor®


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