New drug could reduce tissue damage after heart attack
19 May 2006
UCL scientists have designed a new drug that inhibits the adverse effects of C reactive protein (CRP), a protein that contributes to tissue damage in heart attacks and strokes.
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; this can be exacerbated by CRP. The UCL team previously showed that human CRP increases the severity of damage in experimental models of heart attack and stroke, first identifying CRP as a valid therapeutic target. The present collaborative study has now rationally designed a potent small molecule inhibitor of CRP. …
Professor Mark Pepys, of the UCL Centre for Amyloidosis & Acute Phase Proteins, whose work on CRP has been supported by the Medical Research Council since 1979, said, "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 action for small molecules bound by target proteins. Coupled with knowledge of the structure and properties of CRP, we were able to design the CRP inhibitor.
"We now propose to develop a CRP inhibitor as rapidly as possible for testing in patients with heart attacks. The drug would be given as soon as patients arrived in hospital. If effective, it would reduce the amount of damage in the heart, thus limiting both early mortality and the size of the scar left in the heart.
"Provided adequate support is available, it should be possible to undertake clinical trials of CRP inhibition within a couple of years. If the treatment proves safe and effective, we also aim to investigate its effectiveness in strokes.
"It is likely that CRP contributes to tissue damage in a range of diseases in which CRP levels are greatly increased, and the inhibition of CRP may thus find broad application in medicine." …