Medical researchers today held out promise that a simple injection is being developed to limit the devastating consequences of heart attacks and strokes.
Described by the lead researcher as ‘a fascinating new achievement,’ work has already begun to translate the research into novel clinical therapies.
Professor Wilhelm Schwaeble (pictured) of the Department of Infection, Immunity and Inflammation at the University of Leicester, initiated and coordinated research collaborations with King’s College London, the Medical University of Fukushima, Japan, and the State University of New York to achieve the present breakthrough findings.
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 lectin pathway of complement activation, a component of the innate immune system.
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 ischemia – a temporary loss of that blood supply and the oxygen that it carries. This excessive inflammatory response is, in part, responsible for the morbidity and mortality associated with myocardial infarction (heart attack) and cerebrovascular accidents (CVAs or strokes). Moreover, the work succeeded in finding a way to neutralize this enzyme by raising a therapeutic antibody against it. A single antibody injection in animals has been shown to be sufficient to disrupt the molecular process that leads to tissue and organ destruction following ischemic events, resulting in significantly less damage and markedly improved outcomes.
“This is a fascinating new achievement in the search for novel treatments to significantly reduce the tissue damage and impaired organ function that occur following ischemia in widespread and serious conditions such as heart attacks and strokes,” said Professor Schwaeble. “This new potential therapy was also shown in animals to significantly improve outcomes of transplant surgery and may be applicable to any surgical procedure where tissue viability is at risk due to temporary interruption of blood flow.”
“The main focus of our work was to identify a key molecular mechanism responsible for the overshooting inflammatory response that can cause substantial destruction to tissues and organs following their temporary loss of blood supply, a pathophysiological phenomenon called ischemia/reperfusion injury,” added Professor Schwaeble. “Limiting this inflammatory response in oxygen-deprived tissues could dramatically improve outcomes and survival in patients suffering heart attacks or strokes.”
For more than 7 years, 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 holds exclusive worldwide intellectual property rights to the MASP-2 protein, all therapeutic antibodies targeting MASP-2, and all methods for treating complement-mediated disorders by inhibiting MASP-2. The company has already begun manufacturing scale-up of an antibody for use in human clinical trials.
Illustration: University of Leicester.
University of Leicester News Release (04/19/11)
e! Science News (04/18/11)
Science Daily (04/19/11)
Abstract (Proceedings of the National Academy of Sciences of the United States of America; Vol. 108, No. 18, 7523-7528 (05/03/11))