New Enzyme Discovery Offers Potential Triple-Action Therapy for Obesity, Liver Disease and Heart Disease
Scientists have identified a previously unknown enzyme, dubbed SCoR2, that plays a critical role in fat production, opening the door to a potential new class of drugs targeting obesity, fatty liver disease, and cardiovascular disease simultaneously. The discovery, made by researchers at University Hospitals and Case Western Reserve University in Cleveland, Ohio, could represent a significant advancement in addressing these increasingly prevalent and interconnected health challenges.
Obesity rates continue to climb globally, driven by increasingly calorie-dense diets and more sedentary lifestyles. This rise in obesity is directly linked to a growing incidence of fatty liver disease (Metabolic dysfunction-associated steatohepatitis, or MASH) and heart disease, creating a complex web of health risks. According to the study authors, these conditions are now a leading contributor to illness and early death worldwide.
How SCoR2 Controls Fat Production
The research, published in Science Signaling, details how SCoR2 functions as a “switch” that regulates fat buildup in the body. The enzyme works by removing nitric oxide from proteins that control fat production. Nitric oxide, a naturally occurring gas in the body, normally acts as a brake on fat production in both the liver and fat tissue. When SCoR2 removes nitric oxide, it allows fat production to proceed unchecked.
“In the liver, nitric oxide inhibits the proteins that make fat and cholesterol. In fat tissue, nitric oxide inhibits the genetic program that makes the enzymes that create fat,” explained Dr. Jonathan Stamler, MD, President and Co-Founder of the Harrington Discovery Institute, Distinguished University Professor, and Professor of Medicine and of Biochemistry at University Hospitals and Case Western Reserve University. This suggests that maintaining proper nitric oxide levels is crucial for regulating metabolism.
Blocking SCoR2: Promising Results in Animal Models
To investigate the potential therapeutic implications of this discovery, researchers blocked the function of SCoR2 in mouse models. They employed both genetic methods and a newly developed drug designed to inhibit the enzyme. The results were striking: blocking SCoR2 effectively stopped weight gain and protected the liver from injury. The treatment led to a reduction in levels of unhealthy cholesterol.
These findings suggest that inhibiting SCoR2 could offer a multi-pronged approach to treating these interconnected conditions. Unlike many current therapies that target individual aspects of obesity, liver disease, or heart disease, a drug targeting SCoR2 could potentially address all three simultaneously.
The Path to Clinical Trials
The researchers are now focused on advancing the SCoR2-inhibiting drug toward clinical testing in humans. The process of moving a drug from the laboratory to human trials is complex and rigorous, but researchers estimate this phase could begin within approximately 18 months.
“Our team looks forward to further developing a first-in-class drug to block weight gain and lower cholesterol, with favorable effects on liver health,” Dr. Stamler stated.
Broader Implications and Drug Development Support
The development of this drug is being supported by the Harrington Discovery Institute at University Hospitals, an organization dedicated to accelerating the translation of scientific discoveries into new treatments. The institute has a growing portfolio of medicines in development, with 227 medicines currently in the pipeline, 75 institutions supported, 46 companies launched, and 24 medicines already in clinical trials. Fifteen medicines have also been licensed to pharmaceutical companies.
The discovery of SCoR2 and the development of a potential inhibitor represent a significant step forward in the fight against obesity, fatty liver disease, and heart disease. While further research and clinical trials are necessary, the initial findings offer a promising new avenue for therapeutic intervention.
Recent research has also focused on targeting other enzymes involved in fat metabolism. For example, a drug targeting DGAT2, another liver enzyme, has shown promise in reversing liver damage in patients with MASH, as demonstrated in a Phase IIb clinical trial conducted by researchers at the University of California San Diego School of Medicine . This study, published in The Lancet, found that blocking DGAT2 reduced fat buildup and inflammation in the liver, regardless of weight change.
The ongoing research into enzymes like SCoR2 and DGAT2 highlights the growing understanding of the complex biological processes that regulate fat metabolism and the potential for developing targeted therapies to address these conditions.
