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 LDL levels have little influence on the frequency of death or cardiovascular events observed for the high-risk acute coronary syndrome (ACS) patients who are characterized by extensive vulnerable atherosclerotic plaque burden.
In the study, use of the drug resulted in a maximum HDL cholesterol increase of 50 percent after eight weeks that was sustained throughout the remainder of the 12-week study. Anti-miR-33a/b treatment in the non-human primate model also increased the expression of miR-33 target genes involved in fatty acid breakdown resulting in suppressed triglyceride levels, a finding not previously observed in mice. The decrease in triglycerides was apparent after four weeks and reached a maximum reduction of 50 percent.
This pre-clinical study was the first to demonstrate that inhibiting miR-33a/b has a significant and sustained effect on both circulating HDL and plasma triglyceride levels, Temel said.
These findings indicate that miR-33a and miR-33b are key regulators of cholesterol and fatty acid metabolism, Temel added, and that an anti-miR-33 approach could directly impact atherosclerosis, as well as address important cardiovascular risk factors such low HDL and high triglycerides.
The researchers will next evaluate whether the drug has the ability to stimulate cholesterol movement out of the arteries, where it has accumulated and formed atherosclerotic lesions.
“Coronary artery disease is the number one killer of people in the United States,” Temel said. “It’s a very big problem. The ideal therapy would not only reduce cholesterol accumulation in the arteries by lowering bad cholesterol but also increase the removal of existing cholesterol in the arteries by elevating good cholesterol. The combination of a statin and anti-miR-33 could potentially be this therapy. While there is still a lot of work that needs to be done with this drug before it can ever be used in humans, anti-miR-33 is showing strong potential as a new therapy for reducing coronary heart disease risk.”
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Media Relations Contacts: Jessica Guenzel, .(JavaScript must be enabled to view this email address), 336-716-3487; or Bonnie Davis, .(JavaScript must be enabled to view this email address), 336-716-4977.
Wake Forest Baptist Medical Center is a fully integrated academic medical center located in Winston-Salem, N.C. Wake Forest School of Medicine directs the education and research components, with the medical school ranked among the nation’s best and recognized as a leading research center in regenerative medicine, cancer, the neurosciences, aging, addiction and public health sciences. Piedmont Triad Research Park, a division of Wake Forest Baptist, fosters biotechnology innovation in an urban park community. Wake Forest Baptist Health, the clinical enterprise, includes a flagship tertiary care hospital for adults, Brenner Children’s Hospital, a network of affiliated community-based hospitals, physician practices and outpatient services. The institution’s clinical programs and the medical school are consistently recognized as among the best in the country by U.S.News & World Report.
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Jessica Guenzel
.(JavaScript must be enabled to view this email address)
336-716-3487
Wake Forest Baptist Medical Center