CRP is normally present at trace levels in the blood but its concentration increases sharply in almost all diseases including trauma, infection, strokes and chronic illnesses such as rheumatoid arthritis and Crohn's disease. CRP levels also rise dramatically after a heart attack. Patients with the greatest and most persistent increases in CRP concentration suffer higher mortality, and CRP is always deposited in and around the damaged heart tissue.
Inflammation contributes significantly to the extent of heart attack damage and this can be exacerbated by CRP. The UCL team has previously shown that human CRP increases the severity of damage in experimental models of heart attack and stroke. This first identified CRP as a valid therapeutic target. The present collaborative study has now rationally designed a potent small molecule inhibitor of CRP.
The new compound, bis(phosphocholine)-hexane, is bound by CRP, inhibits all CRP functions in the test tube, and blocks the tissue damaging effect of CRP in an experimental heart attack model.
Professor Mark Pepys, of the UCL Centre for Amyloidosis and Acute Phase Proteins, whose work on CRP has been supported by the Medical Research Council since 1979, says: "Although heart attacks are responsible for about one third of all deaths in developed countries, most patients survive a first heart attack. However, if they have a large scar, patients go on to develop heart failure which is eventually fatal. Reducing the immediate damage is thus critically important.
"We had previously invented a new mechanism of drug
Source:University College London