Calls Now Open
2027 Scholar-Innovator and ADDF-Harrington
Cardiovascular, Inflammation, Metabolic, Transplantation
Targeting Non-Coding RNAs to Treat Atherosclerosis
2024 Harrington Scholar-Innovator
Many people are familiar with statins, a class of drugs widely used to prevent accumulations of harmful cholesterol plaques in the coronary arteries. Yet despite decades of use and millions of prescriptions for statins, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide.
“Statin medications are inexpensive and effective, but there are still many people developing atherosclerosis, having heart attacks and dying from coronary heart disease,” Dr. Holley says. “So we’d love to have another tool to treat atherosclerosis that’s independent of treating cholesterol.”
This goal has led Dr. Holley and his colleagues to discover that certain small nucleolar RNAs (snoRNAs,) a class of RNA molecules that guide chemical modifications of other RNAs, are critical for atherogenesis. Further, in multiple mouse models, they found that selectively shutting down specific snoRNAs strongly mitigated atherosclerotic development
regardless of serum cholesterol levels.
During their research, Dr. Holley and his team discovered that snoRNAs are not easily targeted by small molecule pharmaceuticals. They overcame this challenge by using antisense oligonucleotides (ASOs), an emerging class of drugs based on nucleic acid, to target snoRNAs for degradation.
Dr. Holley notes that because snoRNA-targeting ASOs are distinct from all other existing and emerging atherosclerosis therapies, there is no reason for them to compete with established therapies such as statins.
“Instead, our proposed therapeutic could serve as a co-first-line option for essentially all patients with ASCVD, including the more than 200 million patients worldwide currently taking statins,” he says.
"There aren't many nucleic acid therapeutics that have been approved by the FDA. Getting expertise and insights from people like our Harrington advisors, who have done nucleic acid drug development, has been incredible."