Animal model suggests simple injection could limit damage from heart attacks and strokes

Research published this week could pave the way for new treatments to reduce the tissue and organ damage that follows the loss of blood supply in heart attacks and strokes, and could improve the outcome of transplant surgery.

An international team led by Professor Wilhelm Schwaeble from the University of Leicester, with long-term support from the Wellcome Trust and the Medical Research Council, has found that the inflammatory response that follows the loss of blood supply to organs and tissue is the main factor in determining the subsequent loss of tissue and organ functions.

In a study published online in the ’Proceedings of the National Academy of Science USA’, Professor Schwaeble and collaborators identified an enzyme, mannan-binding lectin-associated serine protease-2 (MASP-2), that is found in blood and is a key component of the innate immune system known as the lectin pathway of complement activation.

The lectin pathway is responsible for the potentially devastating inflammatory tissue response that can occur when any bodily tissue or organ is reconnected to blood supply following a temporary loss of that blood supply and the oxygen that it carries. This excessive inflammatory response is, in part, responsible for the damage caused by heart attacks and strokes, and limiting it could dramatically improve outcomes and survival in patients.

The researchers were able to neutralise the response in mice using a single antibody injection, disrupting the molecular process that leads to tissue and organ destruction. This resulted in significantly less damage and markedly improved outcomes. The therapy also has the potential to significantly improve outcomes of transplant surgery and may be applicable to any surgical procedure where tissue viability is at risk because of temporary interruption of blood flow.

The research may make it possible to develop a simple injection able to limit the devastating consequences of heart attacks and strokes.

The University of Leicester team has been working closely with a commercial partner, Omeros Corporation in Seattle, USA, to develop therapeutic antibodies for research and clinical applications. Omeros has already begun manufacturing scale-up of an antibody for use in human clinical trials. It is anticipated that the first clinical trials of the human antibody in people who have had heart attacks will be conducted in the Leicester Biomedical Research Unit, at Glenfield Hospital, Leicester.

Schwaeble WJ et al. Targeting of mannan-binding lectin-associated serine protease-2 (Masp2) confers a significant degree of protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc Natl Acad Sci USA 2011 [epub ahead of print].