New Drug Uses Gene Method to Cut Cholesterol-Maker

A new type of cholesterol-lowering drug can reduce levels of blood fat by more than 55 percent, the makers of the drug reported on Wednesday.

A new type of cholesterol-lowering drug can reduce levels of blood fat by more than 55 percent, the makers of the drug reported on Wednesday. The drug works through an experimental genetic method called antisense, said Carlsbad, California-based Isis Pharmaceuticals . Known only by its experimental name, ISIS 301012 interferes with a protein called apoB-100. ApoB-100 is the molecular carrier of low density lipoprotein and very low density lipoprotein cholesterol, the so-called bad cholesterol that causes heart disease. Doctors believe that inhibiting ApoB would be a good way to lower cholesterol but so far it has been hard to do. No drug has been found that will affect it. Isis researchers tried a new method called antisense, which uses a kind of molecular plug to stop a gene from working. Antisense compounds have to be injected but have proven a promising approach to several diseases. Isis announced results on the first 19 volunteers in its trials of the drug. After 25 days of treatment, the volunteers getting the largest doses had their total cholesterol go down by between 7 percent and 36 percent, the company said in a statement. LDL levels fell by between 27 percent and 44 percent. “These data represent a landmark achievement in the cardiovascular field as they are the first to correlate specific inhibition of apoB-100 with substantial reductions in cholesterol in humans,” said Dr. Stephen Young of the University of California San Francisco, who advises Isis. Dr. Steve Haffner of the University of Texas Health Science Center, San Antonio, said statin drugs work well to lower cholesterol but many patients still have high cholesterol levels after taking them.”Statins might lower LDL by 50 percent,” Haffner said in a telephone interview. “There is clearly a need for additional agents.” Haffner, an expert in heart disease and diabetes who was not involved in the study, said some patients also get severe side-effects from statins, including a condition that causes muscle pain. “Not every patient tolerates statins,” he said. Lowering cholesterol reduces the risk of stroke, heart attack and hardening of the arteries or atherosclerosis.(Source: Reuters Health News: Maggie Fox: August 2004)