Promising New Sepsis Treatment is on the Horizon

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A promising new drug for sepsis is on the horizon thanks to new funding from the British Heart Foundation, which could help take the laboratory discovery into the clinic. The first clinical trials of a treatment for deadly septic shock will only be possible if these studies, led by Dr. James Leiper at the Medical Research Council Clinical Sciences Centre (MRC CSC), take place.

James Leiper has a "highly promising" new approach to treating sepsis. Photo courtesy of MRC Clinical Sciences Centre

A promising new drug for sepsis is on the horizon thanks to new funding from the British Heart Foundation, which could help take the laboratory discovery into the clinic. The first clinical trials of a treatment for deadly septic shock will only be possible if these studies, led by Dr. James Leiper at the Medical Research Council Clinical Sciences Centre (MRC CSC), take place.

Sepsis, a life-threatening condition caused by an infection, leads to more than 100,000 people being admitted to hospital in the UK each year. But more than one-third (around 37,000) of those people die. Antibiotics can effectively treat the infection but the body’s response to the infection can cause dangerously low blood pressure, organ failure and death. An effective treatment for this aspect of sepsis is urgently needed and many drugs have already failed to make it through clinical trials.

The BHF Translational Award, part of the charity’s new research strategy launched last month, granted to Dr. James Leiper and his clinical collaborator Dr. Simon Lambden at the MRC CSC, will cover the costs of further studies to find different forms of a drug candidate they are developing to treat the dangerous effects of sepsis. One of these new forms could then be taken into clinical trials.

Early funding for the research, awarded back in 2002, also came from the BHF. This funding supported the laboratory animal research where the discovery was made of the potential of a drug called L-257. It works by reducing the production of the chemical nitric oxide. Healthy amounts of nitric oxide are needed for the normal function of blood vessels. However, during sepsis high nitric oxide levels can cause dangerously low blood pressure and ultimately organ failure.

In animals L-257 has been shown to improve survival and reduce organ failure during sepsis. The researchers are confident it will be safe and effective at treating sepsis in people.

Leiper, who is leading this new BHF-funded research at the MRC CSC, says, “Developing treatments for sepsis has been called the ‘graveyard for pharmaceutical companies’ because people with sepsis are often in a highly unstable condition. This can make it very difficult to detect whether a treatment is working. Therefore clinical trials for sepsis treatments often end up being very large and very expensive. But with the BHF’s support we should be able to reduce these risks, and make L-257 a very attractive product for taking into clinical trials. After over a decade of hard work in the lab, it’s exciting to see this promising drug is getting closer to helping thousands of people a year.”

Paul Cornhill, aged 55, from Tamworth in Staffordshire, suffered sepsis and septic shock in 2012 and spent nearly five weeks in hospital as a result of the condition. He survived this traumatic experience but he still feels debilitated by the after effects. The researchers hope the L-257 drug will not only save lives but reduce the long term complications caused by sepsis.

“I’m so grateful to be alive but it’s three years later and I still feel the effects of what I went through," Cornhill says. "I am getting stronger but I often struggle to climb stairs without feeling weak or breathless. We need new, more effective treatments for sepsis that save lives and also mean people recover quicker from the condition. I was ill in hospital for a long time and my recovery has been even longer, but with the support of Good Hope Hospital, the Sepsis Trust, my wife and daughter, I’m finally beginning to feel like myself again.”

Professor Peter Weissberg, medical director at the British Heart Foundation, says, "We’ve recognized in our new research strategy that there can be many obstacles preventing exciting laboratory discoveries from benefiting patients. We launched our Translational Awards to provide researchers with the funding they need to carry out work that can help them overcome those obstacles and attract the substantial investment needed to make a new drug or test available for patients. It’s not realistic for charities to take on the costs and risk associated with taking a new drug or test through clinical trials. But we can help make lab research, like Dr. Leiper’s which we’ve funded over many years, attractive enough for pharmaceutical companies to take on that risk and cost.”

BHF-funded research has helped make significant advances in the prevention, diagnosis, and treatment of cardiovascular disease. Since the BHF was founded in 1961 the number of deaths from cardiovascular disease in the UK has more than halved. However, there is much more to do and the BHF’s new five year research strategy will only be deliverable with the continued generosity of the UK public.

The BHF’s Translational Awards have been introduced to support the pre-clinical development of new cardiovascular medicines and technologies so that they are attractive for follow-on funding. The award will help to bridge the funding gap between promising innovations and the clinic with the aim of accelerating advances in cardiovascular science for patient benefit.

Source: MRC Clinical Sciences Centre/Institute of Clinical Sciences (ICS) Faculty of Medicine, Imperial College London 

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