Inflammation represents a normal host response to a variety of stimuli. Although this response is crucial to survival, a number of serious and debilitating diseases are associated with defective control or initiation of the inflammatory process. Rheumatoid arthritis is one well known and difficult to treat inflammatory condition. Characterized by chronic and nonspecific inflammation of the peripheral joints, this disease can cause the progressive destruction of articular and periarticular structures. About 1% of all populations are affected by this condition, women two to three times more often than men This translates to a total of 5 million in the major pharmaceutical markets, a figure that is likely to rise to approximately 5.7 million in 2010. Although disease progression can usually be controlled, 10% of patients are eventually severely disabled despite full treatment. The market for agents used to treat rheumatoid arthritis totaled $1.6 billion in 2000 however this figure is expected to rise significantly. A second inflammatory disease that is on the rise is Asthma which is now thought to affect 155 million people worldwide. In the United States alone there has been a two-fold increase in the number of cases of Asthma. Consequently, the market is large standing at $8 billion worldwide. Despite a large number of drugs available to clinicians, up to 15% of patients suffer from uncontrollable disease symptoms, increasing the demand for novel therapies that possess new modes of action. Cyclosporin A is an immunosuppressant which was launched almost 20 years ago by Novartis. This drug is now used in a variety of inflammatory diseases including rheumatoid arthritis, dermatitis/psoriasis and inflammatory bowel disease, as well as in transplant recipients. Under specific circumstances cyclosporin A has also been used as an alternative/steroid sparing treatment of asthma. Cyclosporin A acts by binding to the intracellular protein cyclophilin. This complex then interacts with intracellular signaling proteins such as calcineurin. German scientists have now identified a new compound, D-43787 which also binds to cyclophilin exerting promising Th2-selective modulatory properties. Mirroring this in vitro activity, D-43787 potently inhibited late-phase airway eosinophilia in actively sensitized and challenged guinea pigs and Brown-Norway rats and reduced edema development in experimental arthritis. The potency of D-43787 was comparable with that of indomethacin and dexamethasone. The mode of action of D-43787 is distinct from that of Cyclosporin A since it failed to affect the activity of calcineurin. Further development of this interesting molecule is awaited.

Link to journal abstract:

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk