EU invests 10.7 million Euro on EICOSANOX – a top-ranking project led from Karolinska Institutet

A decision has now been taken on the grant that the EU’s Sixth Framework Programme is to provide for EICOSANOX, a major research project coordinated by Karolinska Institutet’s Professor Jesper Z. Haeggström. The project, which ranked highest in its category, is an Integrated Project (IP) and is to be allocated research funding of 10.7 million euro over the course of five years. A total of 15 research groups from six European nations will be merged into a very large multi-disciplinary consortium, including a team from Canada and two biotech companies. The research is focused on prostaglandins, leukotrienes and nitric oxide, all of which are central to widespread diseases like cardiovascular disorders, atherosclerosis, dementia and cancer.

Several components of the project have given the EU cause to rank this project high:

• Relevance – it concerns important disease groups that are responsible for the majority of all deaths in Europe.
• European expertise – there is already unique expertise in Europe equal to the best in the USA and Japan.
• It has clear commercial potential, something which is given priority in the EU’s Sixth Framework Programme.

The research examines the enzyme systems that govern the formation of certain signal substances in the body, particularly derivatives of arachidonic acid. These substances control the course of events during inflammation and fever as well as blood coagulation and cellular growth. They are therefore of significance to several major disease areas, such as cardiovascular diseases, dementia and cancer. If scientists learn how to control these signal substances, they may be able to find suitable therapies. The annual global sales of drugs in these therapeutic areas have been estimated to more than 100 million Euro.

“I’ve hand-picked every single group involved,” says Professor Jesper Z. Haeggström, who is leading the consortium from Karolinska Institutet. “All of them are at the forefront of their specialist research fields.”

The consortium brings together research groups from Sweden, Germany, Italy, United Kingdom, Ireland and Spain, with three different specialisations: COX, LOX and NOS, abbreviations that stand for three different enzyme systems and their products. The systems and their functions are intimately integrated in the body, and the objective of the project is for the groups to meet and pool their knowledge. One important goal is to identify new genes that are involved in the regulation of COX, LOX and NOS, and that can be used to develop new drugs.

Enzymes of the COX family regulate the formation of prostaglandins from arachidonic acid (a fatty acid). “We block this system every time we take a normal aspirin, and this is also where the controversial COX-2 inhibitors, VIOXX and Celebrex, have their effect,” continues Professor Haeggström.

The second enzyme type, LOX, is necessary for the formation of leukotrienes, which are also derived from arachidonic acid. Important drugs have been produced in this area too, in particular the anti-leukotrienes that are used in the treatment of asthma and allergic hay fever. The third specialisation involves NOS, the enzyme active in the synthesis of nitric oxide, the central role of which has become all the more noted recently. The system is affected, for instance, during nitroglycerine therapy for angina and on the treatment of impotence with the now infamous Viagra.

Apart from four groups at Karolinska Institutet, the network formed through the consortium includes the University of Frankfurt, which has research groups in all three areas. Cardiologists from Italy’s D’Annunzio University are also involved, along with British researchers from the renowned William Harvey Institute and Salvador Moncada, one of the world’s most eminent researchers in the field of nitric oxide. The Canadian group is specialised in animal models for studies of eicosanoids. Two biotech companies, the Swedish Biolipox AB and the Franco-Italian NicOx, are also taking part.

Research into prostaglandins and leukotrienes (also known as eicosanoids) has long been a flagship field of research in Sweden and one in which we have led the world. The substances were discovered at Karolinska Institutet, which earned Sune Bergström and Bengt Samuelsson, together with John R. Vane from England, the Nobel Prize in Physiology or Medicine in 1982.

“Karolinska Institutet has trained many of today’s leading Japanese and American researchers in eicosanoids,” says Professor Haeggström.

The consortium includes four groups from Sweden and Karolinska Institutet:

• Professor Haeggström’s team at the Department of Medical Biochemistry and Biophysics, specialising in preclinical basic research into eicosanoids and the COX and LOX enzyme systems.
• Jon Lundberg’s team at the Department of Physiology and Pharmacology, specialising in nitric oxides and their role in the body’s immune systems.
• Göran K. Hansson’s team at the Department of Medicine at Karolinska University Hospital in Solna, specialising in clinical research into atherosclerosis and vascular inflammation.
• Pär Nordlund’s team, which has recently moved to Karolinska Institutet and the Department of Medical Biochemistry and Biophysics in order to work with determination of protein structures by X-ray crystallography at large scale.

“For us at Karolinska Institutet, this grant provides valuable long-term basic support at a time when national medical research funds have been completely drained,” says Professor Haeggström. “Each one of the four KI groups will receive between 50 000 and 200 000 Euro per year for five years, and we’ll also be getting extra resources for the administration and coordination of the consortium.”