UBC study on mice finds ‘major breakthrough’ in new blood thinner with no increased risk of bleeding

Canadian researchers have helped develop what they say could be a safer, more effective blood thinner that prevents clots without increasing the risk of bleeding.

Scientists at the University of British Columbia, together with researchers at the University of Michigan, published a study Wednesday in the journal Nature Communications about their work using a new compound, called macromolecular polyanion inhibitor or MPI 8, which they describe as a “groundbreaking discovery.”

The researchers say their preclinical studies were effective in preventing blood clots in mice, without increasing the risk of bleeding, and showed no signs of toxicity even at high doses.

However, they say MPI 8 requires more research to show it is safe and effective in humans.

“The development of MPI 8 represents a major breakthrough in the field of blood clot prevention and treatment,” 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 in a news release.

“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.”

A clot forms when parts of the blood thicken and form a semi-solid mass. These clots can then travel to other parts of the body and lead to serious conditions if untreated such as deep vein thrombosis, heart attack, pulmonary embolism and stroke.

While blood thinners, also referred to as anticoagulants and antithrombotic drugs, can help prevent clots, there is a risk of bleeding.

The researchers say existing blood thinners target enzymes that are essential for clotting but must be carefully dosed and monitored, as a result, due to their impact on the normal clotting process required to heal wounds.

The researchers instead decided to target polyphosphate, a molecule that helps accelerate blood clotting but is not essential.

MPI 8, they say, has “smart” binding groups with positive charges that attract to polyphosphate’s negative charge — binding and inhibiting it, while leaving other negatively charged cells and proteins alone.

“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 per cent of the action of the polyphosphate,” Jim Morrissey, a professor of biological chemistry and internal medicine at the University of Michigan, said.

“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.”

The scientists say both universities have filed a patent application for the technology.