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Researchers Explore Innovative Treatment Targeting Blood Clots Without Increased Bleeding Risk
A pioneering breakthrough made by experts at UBC and the University of Michigan, revealed in Nature Communications, may lead to the development of blood thinners that are both more secure and efficient.
Through the amalgamation of their knowledge in chemical synthesis and blood clotting systems, the researchers have created a novel substance called MPI 8, which has the potential to prevent blood clots without heightening the risk of bleeding, a prevalent adverse effect of current blood thinners.
Dr. Jay Kizhakkedathu, a professor and Canada Research Chair at UBC's department of pathology and laboratory medicine, as well as the UBC Centre for Blood Research, stated, "The invention of MPI 8 is a significant breakthrough in the realm of blood clot prevention and treatment. By selectively targeting a specific molecule involved in clot formation without disrupting the natural clotting mechanism, we have developed a blood thinner that has demonstrated greater safety and efficacy in animal studies, with tremendous potential to enhance the quality of human life."
Additional investigations will be required to validate the safety and effectiveness of MPI 8 in human subjects, but preliminary outcomes provide optimism for a new epoch in blood clot prevention and thrombosis management, as well as demonstrating the potency of collaborative research in medicine.
Blood clots pose a severe health risk, impacting numerous individuals worldwide. If not addressed, they can lead to life-threatening conditions such as pulmonary embolism, deep vein thrombosis, stroke, and heart attack.
While blood thinners, also known as anticoagulants or antithrombotic drugs, are crucial in preventing and treating blood clots, they bear a considerable bleeding risk. This factor can result in complications and restrict their use in certain patients.
Current blood thinners, such as heparin, warfarin, and direct oral anticoagulants (DOACs), operate by targeting crucial enzymes in blood clotting. Nonetheless, their administration necessitates close monitoring and dosing since inhibiting those enzymes can disrupt the natural clotting process necessary for wound healing.
In contrast, UBC and Michigan scientists adopted an innovative strategy to aim at polyphosphate, a molecule involved in blood clotting that expedites the process but is not a requisite for it.
Dr. Jim Morrissey, a professor of biological chemistry and internal medicine at the University of Michigan, whose research has highlighted the function of polyphosphate in blood clotting, stated, "Our hypothesis was that targeting polyphosphate with an antithrombotic drug could be safer because it would only slow down the clotting reactions, even if we completely eliminate the action of polyphosphate." "To target it in a highly innovative way compared to conventional clotting medications, we needed the expertise of Dr. Kizhakkedathu's lab," he added.
The Kizhakkedathu laboratory developed a collection of potential molecules and scrutinized them to select a candidate that meets the necessary criteria, ultimately pinpointing MPI 8. This exceptional molecule features "smart" binding groups with positive charges that are attracted to polyphosphate's negative charge. It will fasten to polyphosphate and restrain it, while sparing the body's other negatively charged cells and proteins, thus preventing hazardous side effects.
In preclinical trials conducted on mice, MPI 8 exhibited exceptional efficacy in preventing blood clots without elevating the risk of bleeding. The drug demonstrated no toxicity symptoms, even at high doses.
Dr. Chanel La, who participated in the project as a chemistry PhD student in the Kizhakkedathu laboratory, stated, "The drug not only exhibits potential as a safer and more efficient alternative for patients, but the design framework used to create MPI 8 is adaptable, which could result in the development of additional compounds with similar properties and effectiveness." "If our research continues to generate favorable outcomes, I would be eager to initiate a sanctioned clinical trial for MPI 8 and bring this medication one step closer to reality for patients requiring it," she added.
UBC and the University of Michigan have filed a patent application for the technology.
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