Thyroid Analogue Reduces Cholesterol without Heart, Bone Risks

An experimental thyroid drug reduces cholesterol without the troublesome side effects experienced by some people on statins, according to a study published in the New England Journal of Medicine. An international team of investigators at Johns Hopkins Medical Institutions, the Karolinska University Hospital and Institute, and the Feinstein Institute for Medical Research tested a substance called Eprotirome in patients with high cholesterol.

Following 189 people with high cholesterol over a three-month period, they observed that it lowered cholesterol levels without the classic thyroid risks to the heart and bone. The study was supported by Karo Bio in Sweden, a company that is developing the drug for its cholesterol-lowering effects.

Over three decades, Irwin Klein, MD, an endocrinologist at the Feinstein Institute, has been at the forefront of researching the connection between thyroid and heart health. It seemed that people with underactive thyroid glands also had high cholesterol levels. These high cholesterol levels were dramatically reduced with thyroid hormone replacement. But the problem in using thyroid hormone for cholesterol lowering is the side effects of an overactive thyroid gland: people can become anxious and have heart palpitations, muscle weakness, and bone thinning.

Scientists spent years trying to develop thyroid analogs that lowered lipids without unwanted side effects. American scientists, including Dr. Klein and John D. Baxter, MD, a senior member of the Methodist Hospital Research Institute, have been working with Karo Bio scientists to solve this problem. They landed on one in particular that lowered cholesterol without any of the problems with the traditional thyroid medicines. Phase I studies showed the drug to be safe.

In the current Phase II study, they reported that it was both safe and effective in lowering cholesterol. What is not known from this study is whether this lowering of cholesterol will ultimately protect patients from heart disease. Dr. Klein said he thinks it may work to reduce cardiovascular disease.

“Every percentage that you lower cholesterol, you lower the risk for heart disease,” he said. “High cholesterol is the single most modifiable risk factor.” About one in three people have cholesterol levels that are higher than the national guidelines set by federal agencies.

Jens Kristensen, a scientist at Karo Bio and the lead author on the study, and his colleagues also found that the experimental medicine lowered a cholesterol product in the blood called lipoprotein A, which is damaging to the heart. There are no available medicines that lower lipoprotein A and Eprotirome lowered the levels by 33 percent.

Since cholesterol lowering is a surrogate marker for heart disease, the scientists will have to conduct other studies to test whether it does in fact reduce heart disease. The next phase of testing must include larger numbers of patients. If the results hold, it could ultimately be used as an alternative to statins. A small percentage of patients can’t take statins, either because they don’t work to lower cholesterol for them or they suffer from unrelenting side effects such as muscle pains, myopathy, and tiredness.

Source: North Shore-Long Island Jewish Health System