Antibody injection could limit inflammation damage from heart
attacks and strokes
3 May 2011
A simple injection of an antibody could limit the devastating
inflammatory response following restoration of blood supply after heart
attacks and strokes.
An international team identified an enzyme, MASP-2 (mannan
binding lectin-associated serine protease-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 ischaemia — 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).
The research team succeeded in finding a way to neutralise 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 ischaemic events, resulting in significantly
less damage and markedly improved outcomes.
Differences in infarct sizes (white areas of
heart sections) between mice of the same litter that have MASP-2 in
their blood (WT) and those that don’t (MASP-2 -/-). In absence of
MASP-2, the damage to the heart caused by transient loss of blood
supply is smaller.
The research has been published in the Early Online Edition of
the Proceedings of the National Academy of Science (PNAS) .
Professor Wilhelm Schwaeble of the Department of Infection, Immunity
and Inflammation at the University of Leicester, initiated and
co-ordinated research collaborations with King’s College London, the
Medical University of Fukushima, Japan and the State University of
“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 ischaemia 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 ischaemia/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 seven 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
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.
Professor Schwaeble’s team and Omeros are also working with
Professor Nilesh Samani, the British Heart Foundation Professor of
Cardiology and Head of the Department of Cardiovascular Sciences at
the University of Leicester.
It is anticipated that the first clinical trials evaluating
Omeros’ human antibody in myocardial infarction patients will be
conducted in the Leicester Biomedical Research Unit , at Glenfield
1. Schwaeble QJ, et al. Targeting of mannan-binding
lectin-associated serine protease-2 confers protection from
myocardial and gastrointestinal ischemia/reperfusion injury.
Proceedings of the National Academy of Science (PNAS). Published
online 18 April 2011