The blockage of white blood cells in the antiphospholipid syndrome has reduced blood clots

ANN ARBOR, Mich. – Anticoagulants are the main treatment option for men and women with antiphospholipid syndrome (APS).

"Unfortunately, treatment with anticoagulants does not prevent any cases of blood clotting in the APS," says Jason Knight, M.D., Ph.D., badistant professor of rheumatology at Michigan Medicine. APS is an autoimmune disease characterized by blood clots in both bades and by a loss of pregnancy in women.

"And these anticoagulants have very little impact on the neurological, hematological and cardiac complications that regularly affect patients with this disease," he adds.

Knight's lab is currently pursuing the idea that anti-inflammatory therapy may be a more targeted way to treat APS and give patients better control of the disease with fewer side effects.

"Specifically, we have been interested in the role that neutrophils play in the PSA, the most abundant white blood cells circulating in the body," said Knight. "Previous studies have shown that neutrophils release spider web-like sticky structures, called extracellular neutrophil traps, also known as NETs, ​​that trigger blood clotting in patients with PPS."

Knight and his team build on this earlier work in a new study published in Nature Communications, who studied two drugs and their effects on NETs in mice with PSA.

"We investigated a novel strategy for the inhibition of these neutrophils, using the experimental drug CGS21680 and an approved drug called dipyridamole," said Knight, lead author of the study.

Using mouse models with APS, the research team first administered CGS21680 and found that it was reducing NET levels in their blood.

"The drug works by activating the adenosine receptors on the surface of neutrophils," says Ramadan Ali, Ph.D., a member of Knight's lab and lead author of the study. "Adenosine is better known for its role in energy metabolism, but also has anti-inflammatory effects when it is released outside the cells.This seems to be a natural way to extinguish inflammation . "

The research team observed that the drug also dramatically reduced the tendency of mice to form blood clots in large veins.

"The testing of this specific drug has allowed us to show that the activation of adenosine receptors is an effective strategy to prevent the release of NET in the APS, as well as in d '. other contexts, "said Ali. "We have also found that the adenosine receptor pathway can be exploited to prevent the formation of blood clots."

Since CGS21680 is not approved for use in humans, the research team also decided to test dipyridamole, a stroke drug, which has already been shown to be effective in activating adenosine receptors. .

"It was very gratifying to see that dipyridamole was copying the results of the experimental drug with which we started the study," says Ali. "This reduced both the release of NET and the tendency of APS mice to form clots."

Although all the work was preclinical, the research team thinks that it could be applied to patients with SAP.

"That's what's exciting," says Knight. "We have identified here a pathway already influenced by a number of drugs approved for use in humans.In addition to dipyridamole, drugs such as apremilast, used in patients with psoriasis and psoriatic arthritis, and methotrexate, used for the treatment of rheumatoid arthritis and certain types of diseases, cancer, can also modulate the adenosine receptor signaling. "

He adds, "Translating these results into clinical trials on patients could therefore be very simple."

Based on their findings, the research team plans to launch a pilot clinical trial in patients with AS.

"We are very motivated to provide safer, more effective, and more individualized treatments for AS patients we see in our clinic," said Knight. "The hope is that by continuing to pursue anti-neutrophil therapies, we will treat APS closer to its source and thus neutralize all aspects of the disease."

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