New therapy shows promise for treating cardiovascular disease

A new therapy being studied in non-human primates by researchers at Wake Forest Baptist Medical Center and colleagues is demonstrating promise as a potential tool for combating cardiovascular disease by increasing good cholesterol and lowering triglycerides in the blood.

Supported by the National Institutes of Health and the Canadian Institutes of Health Research, the preclinical findings appear in this week's issue of the journal Nature.

"The study was conducted because there is a very strong inverse correlation between the amount of HDL (good cholesterol) and heart disease," said co-principal investigator Ryan Temel, Ph.D., an assistant professor of pathology and lipid sciences at Wake Forest Baptist. "The higher your level of HDL, the lower your risk of developing cardiovascular disease. Currently, however, there are few therapies that significantly raise HDL."

While there are several effective therapies available on the market for lowering LDL, or bad cholesterol, modern medicine has yet to find a good way to raise HDL, Temel said. "Even if you take a statin or some other therapy to lower your LDL, the risk of having coronary heart disease is still around 50 percent. There's clearly a lot of room left for improvement."

Temel and colleagues from NYU Langone Medical Center and Regulus Therapeutics Inc., a biopharmaceutical company, are studying a new drug that targets microRNA-33 (miR-33). MiR-33 is a small RNA molecule that reduces HDL and increases triglyceride production. In previous studies in mice, the drug has been effective in promoting atherosclerotic plaque regression and increasing HDL.

For the current study, researchers tested the drug, anti-miR-33, in non-human primates and found that it increased HDL cholesterol and lowered triglycerides. Non-human primates were selected this time because rodents only express one form of miR-33 – miR-33a – while humans and non-human primates have two types of miR-33 – miR-33a and miR-33b.

Cardiovascular disease (CVD) is the leading cause of death globally, greater than all causes of cancer combined. It represents an enormous area of unmet need and a commercial opportunity with $35 billion in 2009 global sales from the LDL-lowering segment alone.

According to the World Health Organization CVD is the number one cause of death globally. Each year, approximately 1.4 million people suffer from acute coronary syndromes (ACS) in the US alone. Approximately 795,000 are afflicted with a stroke in the US. Additionally, peripheral arterial disease affects up to 20% of Americans age 65 and older.

Current LDL-focused therapies for CVD only reduce cardiovascular events by 25-35%, leaving significant opportunity for further improvements. Moreover, recent clinical data suggests that observed for the high-risk acute coronary syndrome (ACS) patients who are characterized by extensive vulnerable atherosclerotic plaque burden.