Ohio State discovery of rare genetic mutations could lead to new cholesterol treatment

Sept. 12, 2022
Discovery could lead to a new way to treat high cholesterol.

An unexplained case of severe coronary artery disease in a seemingly healthy young man led scientists at The Ohio State University Wexner Medical Center and College of Medicine to a discovery that could lead to a new way to treat high cholesterol. 

Ohio State scientists discovered rare genetic mutations that had never been identified before and that could cause severe early onset of coronary artery disease, the most common type of heart disease in the United States. The discovery is leading to a better understanding of how cholesterol functions and the possibility of developing safer therapeutics for the 94 million Americans with high cholesterol. 

Marcus Wright of Delaware, Ohio was 27 when he suffered a heart attack and continued to have heart-related problems. Doctors were puzzled after finding out he had severe coronary artery disease despite being active and eating a healthy diet. He was eventually referred to Dr. Ernest Mazzaferri, Jr., an interventional cardiologist at Ohio State’s Richard M. Ross Heart Hospital and a clinical professor of Internal Medicine.

Despite optimal medical therapy, Wright continued to have symptoms and needed multiple heart stents, which are expandable metal coils placed in a blocked blood vessel to keep the arteries open. When both Wright’s mother and younger brother were later diagnosed with severe coronary artery disease, Mazzaferri suspected there was a genetic link. He decided it would be a good case for Ohio State’s JB Project, which is funded by philanthropy and brings together clinicians and scientists to decipher the root cause of highly unusual cases involving coronary artery disease, arrhythmias and heart failure. 

A team of researchers led by Sara Koenig, assistant professor of Internal Medicine, conducted genetic sequencing of Wright’s DNA and identified unique genetic variants that were causing his advanced disease. To better understand the potential implications of these genetic mutations, Koenig expanded her study, identifying the same mutations in his mother, father and brothers. 

The researchers determined that Wright’s genetic variants prevented his good cholesterol from effectively clearing out his bad cholesterol (known as LDL), leading to his advanced coronary artery disease. Their findings were published in the American Heart Association’s Circulation Research.

Researchers examined 788 FDA drugs approved for various diseases to narrow down which ones may promote a healthy HDL function. They are now working on developing different diagnostic tests and a new therapeutic drug that may provide an alternative option for those living with high cholesterol.

The Ohio State University Wexner Medical Center release