Blazing a New Trail in the Treatment of Heart Disease

An injectable nanoparticle that delivers HMG-CoA reductase inhibitors, or statins, which directly inhibit atherosclerotic plaque inflammation could represent a new frontier in the treatment of heart disease. This novel approach is being developed by researchers at Icahn School of Medicine at Mount Sinai, who have seen promising results in mice models and plan to translate their findings to humans within the next few years.

The researchers found that administering injections of the statin nanodrug at a low dose over a three-month period significantly inhibited plaque progression, while the administration of four high-dose injections over the course of a week eradicated 90 percent of the inflammation in advanced atherosclerotic plaques. The results were published in the January 20, 2014, edition of Nature Communications.

“The goal to treating heart disease is targeting inflammation,” says the study’s senior investigator Willem Mulder, PhD, Associate Professor of Radiology and Director of the Nanomedicine Program in the Translational and Molecular Imaging Institute at Icahn School of Medicine at Mount Sinai. “But anti-inflammatory drugs have a lot of side effects. When you put the statin in a nanoparticle and deliver it directly to the site, you prevent it from going elsewhere and creating problems.”

Despite the widespread use of oral statins and preventive strategies to control smoking and high-cholesterol diets, atherosclerotic diseases continue to be a major cause of death and disability worldwide. Even when treatment goals are met, patients have a high risk of a recurring heart attack within the first few years.

The new delivery strategy is based on reconstituted high-density lipoprotein (rHDL) nanoparticles. Orally prescribed statins, which are the current standard of care, are limited by a couple of factors, according to Dr. Mulder. “They reduce lipid levels but don’t resolve inflammation in the vessel wall because their effect is limited by absorption in the liver and by concerns over doses that are too high and cause hepatotoxicity and myopathy.”

Dr. Mulder, who is working with Zahi A. Fayad, PhD, Professor of Radiology and Medicine (Cardiology), and Director of the Translational and Molecular Imaging Institute, says their team is examining the results of combining ingested statins with injected nanoparticles. They are also trying to find compounds that have a longer lasting effect. So far, one important finding was that the rHDL nanoparticle was not seen as a foreign invader by the body’s immune system.

“Levels of inflammation spike after a heart attack, which is why up to 30 percent of patients may suffer another heart attack, some while in the hospital or just after discharge,” says Dr. Fayad. A vital time to prevent the onset of inflammation and stabilize the body through nanotherapy would be immediately following a heart attack or stroke. Nanotherapy could also be used to prevent heart attacks from occurring the first time.

The team also includes researchers at the Academic Medical Center in Amsterdam, Holland, where Dr. Mulder has a secondary affiliation as Professor of Cardiovascular Nanomedicine.

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