“There are those who can’t tolerate high dosages of statins because of adverse side effects and even those who have hereditary problems where statins are just not effective,” said Dr. Christie Ballantyne, professor of medicine and section chief of cardiology and cardiovascular research in the department of medicine at BCM.
Gene varients of PCSK9
One focus is gene varients of PCSK9, which can reduce or increase cholesterol levels. This gene variant has been shown to bind to LDL receptors, preventing them from functioning properly. LDL receptors help to remove bad cholesterol from the blood stream.
“Certain variation of PCSK9, known as gain of function mutations, increase cholesterol levels,” said Ballantyne, who is also the director of the Center for Cardiovascular Disease Prevention at BCM and the Methodist DeBakey Heart Center and co-director of Lipid Metabolism and Atherosclerosis Clinic at The Methodist Hospital. “There is also a genetic variant with a loss of function mutation that lowers LDL levels, so researchers developed a way to knock out the function of PCSK9 and found that it was very effective to lower LDL levels.”
Researchers created PCSK9 antibodies that bind specifically to PCSK9 and prevent them from interacting with LDL, resulting in significant reductions in LDL by more than 50 percent.
“The antibody can be given as an injection once or twice a month. So far, in smaller past studies, we have seen good tolerability and LDL levels going down,” said Ballantyne. “Our goal for the current study is to replicate these results in a larger group, to determine how this treatment works in combination with other treatments and to learn if the inhibitor will work for those who are statin intolerant.”
Additional inhibitor studies
Two other trials are also under way, both involving inhibitors of cholesterol ester transfer protein (CETP). When functioning properly, CETP works to transfer and regulate LDL and HDL levels. However, increased function of CETP has been shown to up the risk of cardiovascular disease. Researchers have been studying a CETP inhibitor called anacetrapib and have shown that it does increase HDL levels while also decreasing LDL levels.
“A past trial (DEFINE) showed that by using anacetrapib, HDL levels were increased by 138 percent and LDL was decreased by 40 percent,” said Ballantyne. “There is also another inhibitor being studied, evacetrapib, that also had similar results.”
Ballantyne’s group, along with other study sites, is now looking into long-term effects and whether these inhibitors will reduce the risk of heart attacks.
For more information on these studies, including qualifications to join, please contact 713-798-3171 or email firstname.lastname@example.org.