In a recent study from Monash University, researchers designed a novel antibody that inhibits one particular blood-borne protein to prevent clot formation, or thrombosis, without potential adverse side effects.
They reported how the novel antibody has been engineered to detect and block the pathological form of the Von Willebrand Factor (VWF) blood protein.
The antibody is able to stop pathological thrombosis that can cause heart attacks and strokes without impacting normal healthy clotting.
The study is published in Haematologica. One author is Dr. Erik Westein.
Heart attack and stroke remain the leading causes of mortality and morbidity worldwide.
Current anti-clotting therapies can and do, cause severe bleeding complications because they also interfere with normal blood clotting.
Four out of five patients who receive antiplatelet therapy still have recurring heart problems.
Existing anti-clotting drugs therefore cannot be used in higher doses. As a result, their efficacy remains disappointingly low and future therapies require a fundamental re-design from the ground up.
In the study, the new approach was to first identify the biological differences between normal blood clotting and pathological blood clotting.
The team found that VWF changes its properties when dangerous blood clots are forming.
Next, they engineered an antibody that only detects and blocks this pathological form of VWF and is therefore only active when a blood clot becomes pathological.
The researchers analyzed the properties of existing antibodies against VWF and identified optimal properties of each that would bind and block VWF under pathological blood clotting conditions.
They then combined these optimal molecular structures into a new antibody to generate a first-in-class drug candidate that has the potential to stop dangerous blood clots without any adverse effects such as bleeding complications.
The team says clinicians presently face a delicate balance of drug efficacy versus bleeding side effects.
But this engineered antibody is purposely designed to not interfere with normal blood clotting so they expect that it can be used at a much higher and effective dose compared to existing therapies.
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