An innovative new treatment targets blood clots without increased bleeding risk, according to new research from North America
By combining their expertise in blood clotting systems and chemical synthesis, the researchers have designed a new compound called MPI 8 that offers the potential to prevent blood clots without any increased risk of bleeding – a common side effect of existing blood thinners.
Dr Jay Kizhakkedathu, a professor and Canada Research Chair at UBC’s Department of Pathology and Laboratory Medicine and the UBC Centre for Blood Research, said: “The development of MPI 8 represents a major breakthrough in the field of blood clot prevention and treatment.
“By targeting a specific molecule involved in clot formation without disrupting the natural clotting process, we’ve created a blood thinner that has proven safer and more effective in animal models, with enormous potential to improve human lives as well.”
Further research will be needed to confirm the safety and efficacy of MPI 8 in humans, but initial results offer hope for a new era in blood clot prevention and thrombosis treatment while serving as a testament to the power of collaboration in research medicine.
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Significant risk of bleeding
Blood clots are a serious health concern affecting millions of people around the world. When left untreated, they can lead to life-threatening conditions such as deep vein thrombosis, heart attack, pulmonary embolism and stroke.
Blood thinners, also known as anticoagulants or antithrombotic drugs, are essential in the treatment and prevention of blood clots but carry a significant risk of bleeding. This can cause complications and limit their use in some patients.
Existing blood thinners such as heparin, direct oral anticoagulants (DOACs) and warfarin work by targeting enzymes that are essential for blood clotting. However, they must be carefully dosed and monitored because disabling those enzymes threatens the normal clotting process required to heal wounds.
UBC and Michigan researchers took an innovative approach to instead target polyphosphate, a molecule involved in blood clotting that accelerates the process but is not essential for it.
Dr Jim Morrissey, a professor of biological chemistry and internal medicine at the University of Michigan whose work has illuminated the role of polyphosphate in blood clotting, said: “Our thought was that polyphosphate might be a safer target to go after with an antithrombotic drug, because it would just slow these clotting reactions down – even if we take out 100% of the action of the polyphosphate.
“We really had to come up with an extremely novel way to target it compared to the usual drugs that target clotting, and that’s where the expertise of Dr Kizhakkedathu’s lab became so important.”
No signs of toxicity
After building a library of potential molecules and screening them for their desired criteria, the Kizhakkedathu lab zeroed in on MPI 8.
This unique molecule has ‘smart’ binding groups with positive charges that are drawn to polyphosphate’s negative charge.
It will bind to polyphosphate and inhibit it while leaving the body’s other negatively charged cells and proteins alone, eliminating toxic side effects.
In preclinical studies, MPI 8 demonstrated remarkable effectiveness in preventing blood clots in mice without increasing bleeding risk. The drug showed no signs of toxicity, even at high doses.
Dr Chanel La, who worked on the project as a chemistry PhD student in the Kizhakkedathu lab, said: “Not only does the drug show promise as a safer and more effective option for patients, but the design platform we used to create MPI 8 is flexible, potentially allowing for the development of additional compounds with similar properties and efficacy.
“Assuming our work continues to produce positive results, I would be very excited to get MPI 8 into an approved clinical trial and bring this drug closer to becoming a reality for patients in need.”
UBC and the University of Michigan have filed a patent application for the technology.
The research is published in Nature Communications.
Image: This scanning electron micrograph (SEM) depicted a number of red blood cells found enmeshed in a fibrinous matrix on the luminal surface of an indwelling vascular catheter; Magnified 2858x. Note the biconcave cytomorphologic shape of each erythrocyte, which increases the surface area of these haemoglobin-filled cells, thereby, promoting a greater degree of gas exchange, which is their primary function in an in vivo setting. In their adult phase, these cells possess no nucleus. What appears to be irregularly-shaped chunks of debris, are actually fibrin clumps, which when inside the living organism, functions as a key component in the process of blood clot formation, acting to entrap the red blood cells in a mesh-like latticework of proteinaceous strands, thereby, stabilising and strengthening the clot, in much the same way as rebar acts to strengthen, and reinforce cement. © Janice Carr. Public domain.