Harrington Discovery Institute at University Hospitals: Advancing Breakthroughs to Transform Medicine for Patients

UH Research & Education Institute

Harrington Discovery Institute at University Hospitals is driving critical advancements in medical research, with two recent discoveries—one in Alzheimer’s disease and another targeting metabolic pathways that influence both weight regulation and cholesterol metabolism. These breakthroughs underscore how Harrington Discovery Institute’s unique translational model bridges the gap between innovative academic research and the development of new medicines for patients with unmet medical needs.

Harrington’s model combines funding, expert drug development guidance, and hands-on project management to de-risk early-stage discoveries and accelerate their path to clinical application. Over the past decade, this model has helped advance hundreds of therapeutic programs toward clinical trials. These efforts highlight Harrington’s core strength: advancing scientific discovery into real-world treatments that address unmet patient needs and improve care.

“By strategically investing in groundbreaking research and providing mentorship and development expertise, Harrington Discovery Institute turns novel scientific ideas into life-changing treatments for patients, offering new hope and more effective options for those in need,” said Jonathan Stamler, MD, President and Co-Founder of Harrington Discovery Institute; Distinguished University Professor; Robert S. and Sylvia K. Reitman Family Foundation Professor of Cardiovascular Innovation at University Hospitals; and Professor of Medicine and Biochemistry at Case Western Reserve University.

From Metabolic Insight to Therapeutic Opportunity

A team at University Hospitals and Case Western Reserve University led by Dr. Stamler (and MD PhD Student Nick Venetos) advanced a foundational biochemical insight into a first-in-class drug candidate for cardiometabolic disease. Investigators identified a novel enzyme, S-nitrosyl-CoA reductase 2 (SCoR2), that regulates nitric oxide signaling on proteins controlling fat synthesis. Their findings show that SCoR2 activity is required for fat production: removing nitric oxide increases lipid synthesis.

Genetic inhibition of SCoR2 prevented weight gain and fatty liver in mouse models and reduced LDL cholesterol. Building on this discovery, the team targeted SCoR2 therapeutically with a small molecule drug—establishing a compelling new approach to treating obesity and high cholesterol.

“These findings point to a new class of medicines that can prevent weight gain, lower cholesterol, and improve liver health,” said Dr. Stamler, senior author of the study.

The work was published in American Association for the Advancement of Science journal Science Signaling. With continued support, the program is now advancing this first-in-class candidate toward clinical trials, positioning the therapy for future evaluation in patients.

Restoring Brain Energy to Reverse Alzheimer’s Disease

A Harrington-supported team has challenged long-held assumptions in neurodegeneration, providing evidence that Alzheimer’s disease may be reversible by restoring cellular energy balance. Investigators from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center identified depletion of NAD+—a critical cellular energy molecule—as a central driver of disease pathology.

Led by Kalyani Chaubey in the Pieper Laboratory, the team demonstrated across multiple models and human brain samples that restoring NAD+ levels can prevent—and even reverse—key features of advanced disease. Notably, delayed treatment improved cognitive function and reversed pathology in mice with established Alzheimer’s, across distinct genetic causes.

“Restoring the brain’s energy balance achieved both pathological and functional recovery,” said Andrew A. Pieper, MD, PhD senior author and Director of the Brain Health Medicines Center at Harrington Discovery Institute.

The study was published in Cell Reports Medicine. Ongoing efforts are focused on advancing this approach toward human clinical trials and evaluating its potential across a broader range of age-related neurodegenerative diseases.

Empowering Researchers to Move Bold Science Toward Patients

Together, these advances demonstrate how Harrington’s integrated operational framework transforms academic insight into therapeutic opportunity. By surrounding researchers with the funding, expertise, and development infrastructure needed to cross the translational divide, Harrington empowers scientists to pursue bold ideas and bring new medicines closer to the patients who need them most.