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Innovative treatment targets blood clots without increased bleeding risk

Safer and more effective blood thinners could be on the way following a ground-breaking discovery by US researchers, that have designed a new compound to target blood clots.

blood clots

The University of British Columbia (UBC) and the University of Michigan, US have combined their expertise in blood clotting systems and chemical synthesis, to design a new compound called MPI 8 that offers the potential to prevent blood clots without any increased risk of bleeding.

“The development of MPI 8 represents a major breakthrough in the field of blood clot prevention and treatment,” said Dr Jay Kizhakkedathu, Professor and Canada Research Chair at UBC’s department of Pathology and Laboratory Medicine and the UBC Centre for Blood Research.

“By targeting a specific molecule involved in clot formation without disrupting the natural clotting process, we have created a blood thinner that has proven safer and more effective in animal models, with enormous potential to improve human lives as well.”

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.

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.

The 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. 

“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 percent of the action of the polyphosphate,” said Dr Jim Morrissey, Professor of Biological Chemistry and Internal Medicine at the University of Michigan.

After building a library of potential molecules and screening them for their desired criteria, the 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.

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.

“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,” concluded Dr Chanel La, who worked on the project as a chemistry PhD student in the lab.

“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.”

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