"The research examines the enzyme systems that govern the formation of certain signal substances in the body, particularly derivatives of arachidonic acid", explained the co-ordinating institute, the Karolinska Institutet in Sweden. "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. 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 at more than 100 million euro", added the institute.
Cardiovascular, cerebral and neoplastic disorders account for the vast majority of deaths in Europe and represent an enormous health problem. The objectives of the project are, therefore, to develop novel strategies for therapeutic interventions and drug design; to create a long-lasting infrastructure for scientific and technical competence; to educate, train and ensure the mobility of researchers; to develop effective mechanisms for technology transfer; and to support the European biotechnology industry in developing new therapeutics in areas of high medical need.
The project brings together 14 research groups from six European countries and Canada, and two biotech companies. Each team is specialised in one of the three different enzyme systems and their products: COX, LOX and NOS. The partners will aim to identify new genes involved in the regulation of these three enzymes that can be used to develop new drugs.
As Jesper Z. Haeggström from the Karolinska Institutet explained, 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", stated Professor Haeggström.
The second enzyme type, LOX, is essential for the formation of leukotrienes, which are also derived from arachidonic acid and cause asthma and hay fever. The third specialisation involves NOS, the enzyme active in the synthesis of nitric oxide. The system is affected, for instance, during nitroglycerine therapy for angina and during the treatment of impotence with the now infamous Viagra.
The major components of the projects are: molecular studies on key enzymes and receptors to elucidate biochemical properties, catalytic mechanisms and structure-function relationships; functional genomics of the Eicosanoid and NO cascades to characterise gene expression profiles under normal and disease states and identification of novel potential drug targets; characterisation of new genes, using proteomics, structural genomics and model organisms; and finally, cell biological work on gene regulation, gene silencing, signalling systems and crosstalk between pathways.
This information will then be used in studies of disease mechanisms in animal models and in clinical investigations, explained the University of Frankfurt, one of the partners in the project. "The basic research together with applied and clinical studies will act in synergy to identify novel targets for pharmacological intervention and drug design for the treatment of patients suffering from cardiovascular, cerebral and neoplastic disorders", concluded the University of Frankfurt.