MPI 8, a unique blood-thinning compound developed by researchers, has “smart” binding groups that inhibit polyphosphate without affecting the body’s other negatively charged cells and proteins.

Blood clots pose a significant health risk to millions of people worldwide, potentially leading to life-threatening conditions such as deep vein thrombosis, pulmonary embolism, heart attack, and stroke if left untreated.

While blood thinners, also known as anticoagulants or antithrombotic drugs, are crucial in preventing and treating blood clots, they can increase the risk of bleeding, which can complicate their use in some patients.

However, a groundbreaking discovery by researchers at the University of British Columbia (UBC) and the University of Michigan, published in Nature Communications, offers hope for the development of safer and more effective blood thinners.

The researchers have utilized their knowledge of blood clotting systems and chemical synthesis to create MPI 8, a novel compound that has the potential to prevent blood clots without increasing the risk of bleeding, which is a common side effect associated with the use of current blood thinners.

According to 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, the development of MPI 8 is a significant breakthrough in the field of blood clot prevention and treatment.

By focusing on a specific molecule involved in clot formation without interfering with the natural clotting process, they have created a blood thinner that has shown to be safer and more effective in animal models.

This discovery holds “enormous potential to improve human lives as well.”

Blood thinners, including heparin, direct oral anticoagulants (DOACs), and warfarin, target enzymes that are vital for blood clotting. However, these drugs require careful dosing and monitoring as they can interfere with the natural clotting process necessary for wound healing.

In contrast, researchers from UBC and the University of Michigan have taken a groundbreaking approach by focusing on polyphosphate, a molecule that speeds up blood clotting but is not essential for the process. This innovative method offers a potentially safer way to prevent blood clots without disrupting the natural clotting process.

“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,” points out 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. “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.”

Following an extensive search of potential molecules and rigorous screening based on desired criteria, the Kizhakkedathu lab identified MPI 8 as the ideal compound. This unique molecule contains “smart” binding groups with positively charged particles that are attracted to the negative charge of polyphosphate.

It specifically targets polyphosphate, inhibiting it while leaving other negatively charged cells and proteins unharmed, thereby eliminating the toxic side effects of existing blood thinners.

In preclinical studies, MPI 8 demonstrated remarkable efficacy in preventing blood clots in mice without causing an increased risk of bleeding. Notably, there were no signs of toxicity even at high doses, indicating the potential for safe use in humans.

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

Although additional research is necessary to ensure the safety and effectiveness of MPI 8 in humans, the promising initial results suggest a potential new era in blood clot prevention and thrombosis treatment.

The success of this groundbreaking discovery serves as a testament to the value of collaboration in the field of research medicine.

Source: 10.1038/s41467-023-37709-0

Image Credit: Getty