Pilot Project

Gwendalyn Randolph
Gwendalyn Randolph, PhD
Associate Professor Gene and Cell Medicine
Mount Sinai School of Medicine

Nicotinamide Riboside as a Novel Therapeutic for Atherosclerosis: Evaluation Using Magnetic Resonance Imaging of Macrophage Migration

Atherosclerosis is characterized by a dominant infiltration of monocytes beneath the endothelial lining of arteries. Following monocyte infiltration and engulfment of lipoproteins by these phagocytes, progression of atherosclerosis is characterized by remodeling of the intimal, medial, and adventitial compartments of major arteries over decades in humans. New treatments for this prevalent disease are continuously sought. In addition to the hurdle of identifying effective new drugs for treatment, the evaluation of drug efficacy itself is a major obstacle limiting progress in the field. Large, decades-long clinical trials for efficacy are a major financial burden, especially considering that some drugs fail to provide the expected clinical benefit. Simple measurement of inflammatory biomarkers in the plasma of patients so far does not comprise a sufficient indicator of clinical responses to therapy. Short-term indicators of efficacy would not replace long-term clinical trials, but would be expected to greatly facilitate the identification of the most promising therapeutics. Since monocyte-derived macrophages are critical mediators of disease, an ideal short-term indicator of effective therapy would be a measureable reduction of monocyte recruitment into or persistence within atherosclerotic plaques, but techniques to readily make such measurements in vivo have been lacking. We propose to develop further a novel MRI-based technology that would allow us to trace monocyte entry and egress from atherosclerotic plaques that could later translate into a system to monitor drug efficacy in patients.