Drug holds promise as treatment for blood poisoning

An international research effort led by Ireland has discovered a way to halt the damage and risk of death caused by blood poisoning. Already tested in mice, the method holds promise for use in humans given it is based on the use of a drug already prescribed for epilepsy.

"This drug protects mice from dying," said Prof Luke O'Neill of Trinity College Dublin who is leading the project. It has potential for use in blood poisoning but also in conditions such as Type 2 diabetes, said Prof O'Neill of the school of Biochemistry and Immunology in the Trinity Biomedical Sciences Institute.

The project involves 10 universities including MIT and Harvard in the US, Sheffield and Glasgow in Britain and also University College Dublin. The research aim was to understand the biochemical processes involved when the body's immune system runs out of control, but yielded much more, Prof O'Neill said.

When bacteria infect a wound and get into the bloodstream they cause a massive response from the immune system, and this causes a huge inflammatory response. The white blood cells responsible for this can get out of control and begin damaging healthy tissues.

The researchers saw that when the white blood cells, macrophages, came into play they used up huge amounts of energy and the team wanted to know more about this by studying the byproducts, he said. “It was never seen before so we went fishing.”

They sampled 790 different byproducts and found that levels of one, called succinate, rocketed by 40 to 50 times its normal amount. High levels of succinate in turn caused the white blood cells to go into overdrive and cause runaway inflammation which can cause death.

They tested the epilepsy drug Sabril to see if this could counter the inflammation and found in mice that it dampened down the succinate and reduced inflammation. "If you give them the drug you can stop them from dying," said Prof O'Neill, who received funding for the research from the European Research Council and Science Foundation Ireland. Details of the work are published online in the journal Nature .

Using a similar approach in humans holds great promise. The fact that the drug is already approved for use in humans also means its use in clinical practice could come more quickly.

“This is an unusual finding and it could have clinical potential,” he said. It will still take some years before trials could begin.