06 Jun 2006   |   News   |   Update from University College London, University of Warwick
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UCL spin-out looks for investment for heart damage drug

A group of researchers, led by Mark Pepys, at University College London has designed and chemically synthesised a new drug, which they have shown to reduce heart tissue damage following a heart attack.

Two CRP pentamers viewed down the fivefold axis, one in red and one in blue, crosslinked by five molecules of bis(phosphocholine)-
hexane (green). Image courtesy Nature.

A group of researchers, led by Mark Pepys, at University College London (UCL) has designed and chemically synthesised a new drug, which they have shown to reduce heart tissue damage following a heart attack. The work was published recently in the journal Nature.

The group now hopes to start clinical development and Pepys has launched a spinout, Pentraxin Therapeutics Ltd, to commercialise the work, and is looking for investment. The company owns the patent for this prospective treatment and other related work.

The drug is a novel small molecule compound called bis(phosphocholine)-hexane that inhibits the adverse pro-inflammatory effects of C-reactive protein (CRP). Trace amounts of this protein are always present in the blood, but its concentration increases dramatically following a heart attack and it binds to the damaged heart tissue.

Pepys’s group previously discovered that, in an experimental animal model of heart attack, injection of human CRP increases damage to heart tissue. Bis(phosphocholine)-hexane blocks this effect, by inhibiting the tissue binding of CRP. The drug has shown efficacy in an animal models.

Around 30 per cent of all deaths in developed countries are caused by cardiovascular disease, which can lead to heart attack. This new compound could help to prevent early deaths from heart attacks, but more importantly, it could reduce the long-term scarring that eventually leads to fatal heart failure by reducing the amount of damage at the time of the attack.

This could complement existing treatments according to Pepys. “The goal of current treatment is to restore blood supply as soon as possible. This is very effective but there is always additional damage caused by the body’s own attempts to clear up the dead tissue. The clearing process involves inflammation which contributes significantly to the final amount of heart tissue that is destroyed,” he said

After identifying CRP as a potential therapeutic target, Pepys developed a high-throughput screen to find existing compounds that would inhibit CRP’s tissue binding. But despite screening 500,000 compounds in the chemical library of a pharmaceutical company none was found to be effective, forcing the UCL group to design the compound from scratch.

“The work highlights the potential of our newly patented platform technology for rational drug design, after failure of the classical high-throughput screen approach,” said Pepys. “It also demonstrates the value of detailed structural information and other knowledge of the drug target.”

High CRP concentration is linked to a number of other diseases. “We have shown that human CRP makes experimental strokes worse and inhibiting CRP may therefore be an appropriate treatment for patients suffering acute thrombotic stroke.”

Other examples of diseases where CRP is implicated are rheumatoid arthritis, Crohn’s disease, serious bacterial infections and trauma, including burns.

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