Philipp Lachenmann: DELPHI Rationale


Ernst Schering Prize 2000

Prof. Dr. Takao Shimizu

On 27 September, 2000 in Berlin, the Ernst Schering Research Foundation will award its Ernst Schering Prize, which this year for the first time is endowed with 100,000 DM, to Professor Takao Shimizu from The University of Tokyo, Japan. The 53-year-old scientist will thus be honored for his pioneering research in the field of eicosanoids, a group of fatty acids that work as signal substances in the body. These transmitters influence, among others, the regulation of blood pressure as well as immune and inflammatory reactions. Researching them therefore fuels the development of new treatment strategies against diseases such as asthma, allergies and imminent organ failure.

Fats, called lipids in "medical jargon," are not only important as energy supply or part of cell membranes in the body. "By now, we do know," Takao Shimizu explains, "that in the signal transmission between cells, these substances play a part in accord with other messenger substances, such as neurotransmitters, hormones and immune transmitters. It is like an orchestra." Shimizu, prize winner of this year's Ernst Schering Prize, has been researching one particular group of these signal substances, called eicosanoids, for 20 years.

However, the prize winner's research has not only yielded surprising facts about the manifold effects of these multi-talents of cellular communication. It also paves the way for new approaches to treat, for example, diseases such as asthma or allergies as well as inflammatory processes or imminent failure of organs in a better and more targeted manner. This is because eicosanoids influence a multitude of processes in the body.

Some examples: They participate in the regulation of blood pressure, blood clotting and the action of the heart, they influence the contraction of the bronchial tubes, they protect the mucous membranes of stomach and intestines against the acids in the digestive juices, they regulate inflammatory and immune reactions, and they also play a role in reproduction.

Perhaps better known than the main "family name," there are two main groups of eicosanoids, called prostaglandins and leukotrienes. Certain prostaglandins influence, among others, inflammatory processes, which can cause pain or fever. Acetylsalicylic acid, better known as Aspirin, inhibits the cyclooxygenases that create prostaglandins. This is the reason why the famous drug works for inflammation, pain and fever.

The second main group of eicosanoids are the leukotrienes. The immune system uses them as messenger substances to regulate inflammatory reactions and specific defenses against pathogenic microorganisms. On the other hand, a "surplus" of leukotrienes can cause an excessive immune response and thus lead to allergic and inflammatory diseases such as arthritis, asthma, or psoriasis, an inflammatory skin disease.

One species of leukotrienes, called LTB4 for short, attracts a certain sort of white blood cells, called "neutrophils," to the location of an infection, and activates them. Together with his collaborators, Professor Shimizu has isolated enzymes that are responsible for the production of the specific leukotriene LTB4. In 1997, the team could also demonstrate the binding site (receptor) to which this leukotriene must bind in order to display its effect. This receptor is called BLT. Until then, all other researchers had failed to achieve this difficult feat - including the Swedish scientist Bengt Samuelsson who in 1982 had been awarded the Nobel Prize for the discovery of Leukotriene B4.

In August of this year, Professor Shimizu and his team reported that they had identified a second receptor for leukotriene B4, so-called BLT2. Since the two receptors occur in different tissues, the scientists believe that their function is different.
Professor Shimizu hopes that antagonists for these receptors may offer new therapeutic options for different diseases. Such antagonists may help to prevent "re-perfusion damage" which occurs when an organ is again supplied with blood after a period of ischemia. This may be important after a myocardial infarction or a stroke, for example, or in acute failure of the kidneys or the lungs. Another chance is that excessive immune reactions in atopic eczema, in psoriasis and in urticaria may be successfully diminished by BLT receptor antagonists. Last not least, graft rejection in transplant recipients could also be reduced.


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