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Credit: CC0 Public Domain
Heart attacks have been the leading cause of death in the United States for the past century. While most heart attack treatments aim to break up blood clots, researchers at Georgia Tech have found a way to prevent blood clots from even forming. Remarkably, their drug has been shown to completely stop blood clots from forming without increasing the risk of bleeding in the body.
Because the drug is affordable and already widely available for other uses, patients may be able to experience these benefits sooner than if they were to wait for an entirely new drug to receive FDA approval. Ultimately, the drug could be used to prevent secondary heart attacks in high-risk patients, as well as primary heart attacks, strokes, and other complications caused by blood clots.
The researchers published their findings in a paper titled “N-acetylcysteine dose-dependently prevents arterial thrombosis in vitro and in mice.” Atherosclerosis, Thrombosis, Vascular Biology.
How blood clots form
Most existing treatments for preventing blood clots contain antiplatelet drugs, which can cause adverse side effects for patients.
“Doctors are caught between a rock and a hard place: They can prescribe drugs that can help prevent a second heart attack, but they can also cause massive bleeding,” says David Ku, the Lawrence P. Huang Endowed Professor in Engineering and Entrepreneurship and the George W. Woodruff Chair of Mechanical Engineering (ME). “These clots are bound together by a protein called von Willebrand factor (VWF), which is another target for drugs.”
VWF is a long protein found naturally in plasma that rapidly forms blood clots. Under normal conditions it acts like an inactive ball of yarn, but when VWF unwinds it becomes sticky and traps platelets.
“VWF captures platelets, which then become activated and release more VWF, which then captures more platelets, creating a positive feedback loop that leads to very fast clot formation,” explains Christopher Bressett, a postdoctoral researcher in ME.
Breaking down blood clots
Bressett and Koo tried to break down the VWF protein using a drug already on the market: N-acetylcysteine (NAC), which is commonly used to treat acetaminophen overdose. Previous researchers have tried to use NAC to break down clots after they form, but Koo’s team tried to stop them before they form.
“We chose NAC because it is currently in clinical use and has a history of safety,” Bressett says. “By using an existing drug off-label, we can shorten the time it takes to start helping patients.”
Researchers at the Petit Institute of Biotechnology and Biological Sciences ran blood through tiny channels that resembled the narrowed arteries that can cause heart attacks and strokes. NAC completely prevented clots from forming under these conditions. The researchers then tested NAC in mouse models and got similar results. Even better, NAC’s effects lasted for six hours after it left the bloodstream, helping keep arteries clearer for longer.
The researchers believe the drug would be most effective when patients have already had a heart attack but are at risk of having a second attack soon after. Intravenous administration of NAC could reduce the immediate risk. Eventually, an orally administered NAC derivative could be given as a daily pill to reduce the risk of heart attacks.
Heart attacks and strokes are just the beginning. Preventing embolisms and other blockages is just the beginning of NAC’s future. Researchers hope to conduct clinical trials and gain FDA approval so that NAC can help patients as soon as possible.
For more information:
Christopher A. Bresette et al, N-acetylcysteine dose-dependently prevents arterial thrombosis in vitro and in mice, Atherosclerosis, Thrombosis, Vascular Biology (2023). DOI: 10.1161/ATVBAHA.123.319044
Courtesy of Georgia Institute of Technology
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