Chemistry Turns Killer Gas Into Potential Cure

Chemists at the University of Sheffield have discovered an innovative way of using targeted small doses of CO which could benefit patients who have undergone heart surgery or organ transplants and people suffering from high blood pressure.

Although the gas is lethal in large doses, small amounts can reduce inflammation, widen blood vessels, increase blood flow, prevent unwanted blood clotting -- and even suppress the activity of cells and macrophages* which attack transplanted organs. The researchers have developed innovative water-soluble molecules which, when swallowed or injected, safely release small amounts of CO inside the human body.

Research carried out in the last decade had already highlighted possible advantages, as CO is produced in the body as part of its own natural defensive systems. However, the problem has been finding a safe way of delivering the right dose of CO to the patient. Conventional CO inhalation can run the risk of patients or medical staff being accidentally exposed to high doses. Now for the first time, thanks to chemistry, an answer appears to have been found.

The new CO-releasing molecules (CO-RMs) have been developed in partnership with Dr Roberto Motterlini at Northwick Park Institute for Medical Research (NPIMR) and with funding from the Engineering and Physical Sciences Research Council (EPSRC).

"The molecules dissolve in water, so they can be made available in an easy-to-ingest, liquid form that quickly passes into the bloodstream," says Professor Brian Mann, from the University's Department of Chemistry, who led the research. "As well as making it simple to control how much CO is introduced into a patient's body, it will be possible to refine the design of the molecules so that they target a particular place while leaving the rest of the body unaffected."

The CO-RMs consist of carbonyls** of metals such as ruthenium, iron and manganese which are routinely used in clinical treatments. They can be designed to release CO over a period of between 30 minutes and several hours, depending on what is required to treat a particular medical condition.

As well as boosting survival rates and cutting recovery times, the new molecules could ease pressure on hospital budgets by reducing the time that patients need to spend in hospital, for example after an operation. They could even help some patients to avoid going into hospital in the first place.

Professor Mann added: "This project provides an excellent example of how non-biological sciences like chemistry can underpin important advances in healthcare."

hemoCORM Ltd, a spinout company set up in 2004 by the University of Sheffield and NPIMR, is now taking the research towards commercialisation. It is hoped that, after further development work, Phase 1 clinical trials can begin in around two years, with deployment in the healthcare sector potentially achievable in around five years.

The 3-year research project 'Development of Carbon Monoxide Releasing Molecules as Novel Pharmaceuticals' ran for three years and received total EPSRC funding of just over £238,000.

Although nearly 500 people have died in the UK over the last 12 years as a result of accidental CO poisoning, small quantities of CO are produced naturally within the human body and are essential to life.

*Macrophage cells are part of the human body's natural defence system.

**A carbonyl is formed when carbon monoxide binds to a metal.