Myriad Genetics Discovers High Cholesterol Gene

06-Jun-2001

Myriad genetics, Inc. (Nasdaq: MYGN), has discovered a human gene responsible for high total cholesterol and low HDL (also known as "good cholesterol"), in individuals with early age myocardial infarction. The research shows that the gene's protein product is produced in abnormal amounts in these individuals and has enzymatic activity and other characteristics that suggest it will be readily amenable as a drug target. The CHD2 (Coronary Heart Disease 2) protein acts in a novel, previously unknown pathway, distinct from the cholesterol synthesis pathway that is acted upon by the statin class of drugs and other classes of drugs.

The CHD2 gene, and its function, was discovered by a combination of genetic analysis of families whose members had heart attacks at an early age and an analysis of biological pathways. In total, more than 5,000 individuals from 145 families were analyzed to identify the gene. The discovery in this population, made by Myriad in collaboration with scientists from the Cardiovascular Genetics Research Clinic at the University of Utah, means that abnormal levels of the CHD2 protein are critical to the development of disease. Because disorders of the CHD2 gene lead to high LDL cholesterol, low HDL cholesterol and early-onset heart disease, inhibition of the gene with a small molecule drug is expected to lower cholesterol and reduce the risk of heart disease across the general population of individuals with high cholesterol. Current therapies, including the statins, are inadequate in lowering the total cholesterol to recommended levels in many patients. Heart disease remains the most common cause of death in the United States. Studies estimate that half of all men and one third of women will develop heart disease during their lives.

"The discovery of this novel drug target for the treatment of heart disease points to the strengths of Myriad's integrated approach to drug development incorporating the best technologies of genomics and proteomics in a high-throughput, industrialized fashion," said Peter Meldrum, President and Chief Executive Officer of Myriad Genetics, Inc. "Myriad now has a full pipeline of earlier stage preclinical compounds to back up our lead prostate cancer drug, which has completed a Phase IIa human clinical trial, and we intend to aggressively advance these compounds toward commercialization."

Studies of the CHD2 gene in animal models have confirmed its role in causing high cholesterol, which is a known risk factor for clogging of the arteries, heart attack and stroke. Myriad is using its ProNet® technology to define the disease pathway surrounding the gene and better understand the function of the CHD2 protein and its role in the biochemical process of the high cholesterol disorder, which leads to heart disease and stroke. Myriad scientists found that the CHD2 gene is not involved in the cholesterol synthesis pathway, but operates in a novel, distinct pathway that leads to both high total cholesterol and low HDL cholesterol. Novel pathway activity provides the potential for a new class of drugs to treat high cholesterol and the accompanying risks of heart attack and stroke. ProNet has proven to be an invaluable tool for both target validation and initial target identification.

"The CHD2 drug target for heart disease is now the focus of a therapeutic development program at Myriad," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "The protein's enzymatic function indicates that it should be possible to block its action with a small molecule drug. Myriad has initiated drug discovery on CHD2 and is creating assays to screen its library of small molecules for a compound with this type of activity."

According to the American Heart Association, 100 million American adults have total blood cholesterol values of 200 mg/dL and higher, and about 40 million American adults have levels of 240 or

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