Overview

Uncontrolled, chronic inflammation is considered a major component of many common diseases, including asthma, atherosclerosis and peripheral vascular disease, Alzheimer's disease, and cancer. These are now understood to be "inflammatory diseases" in the sense that inflammation contributes to disease progression, tissue dysfunction, and ultimately organ failure, but it may not be the causative factor. Pro-inflammatory mediators and biochemical pathways have been widely studied, and recent research has elucidated mediators and biochemical pathways that contribute to the resolution of inflammation, providing new anti-inflammatory targets and drug development opportunities. At a January 25, 2011, symposium at the New York Academy of Sciences titled Novel Mechanisms in the Resolution of Inflammation: Implications in Health and Disease, researchers gathered to reviews recent discoveries in studies of the active resolution of inflammation. These studies have led to new approaches and to resolution pharmacology data for the treatment of inflammatory diseases, including promising first-in-human clinical trial results.

George Zavoico of MLV began the event with an overview of the topic. Ira Tabas from Columbia University then presented an update on mechanisms and consequences of defective inflammation resolution in atherosclerosis, discussing in detail how macrophages die in advanced lesions and the key role of defective efferocytosis, the process by which dead macrophages are normally cleared. He also discussed the devastating downstream effects of plaque necrosis. Charles N. Serhan from Harvard University and Brigham & Women's Hospital discussed novel mechanisms in the resolution of acute inflammation, giving a structural elucidation of specialized pro-resolving mediators (SPMs) and pro-resolving actins. In particular, he discussed the biosynthesis and functioning of three families of lipid-derived chemical mediators: resolvins, protectins, and maresins. From Queen Mary University of London, Mauro Perretti rounded out the first half of the program by discussing the role of other players in the "pro-resolving" phase of the acute inflammation process. Echoing Serhan's desire to harness endogenous resolution mechanisms to treat uncontrolled inflammation, Perretti presented his work on two pro-resolving mediators, Lipoxin A4 and Annexin A1, and their interactions with a specific receptor as they contribute to inflammation resolution.

Karsten Gronert of the University of California, Berkeley, then took the audience on a fascinating journey into eye biology and inflammation, as he discussed ways to stop the transition to chronic inflammation by preventing polymorphonuclear (PMN)-mediated tissue injury. Gronert presented recent findings from his group's investigation into an intrinsic lipid circuit in the cornea that helps resolve inflammation and promote ocular wound healing. Understanding this circuit could be crucial to preventing early-stage dysregulation of inflammatory processes from becoming inflammatory disease. Per Gjorstrup from Resolvyx Pharmaceuticals provided an industry perspective on taking synthetic analogues of resolvins from the bench to the clinic for use as a new therapeutic agent to treat dry eye. His presentation covered the efficacy of dose selection methods, murine models, and in vitro tests, as well as the preparation for a phase 2 clinical trial of the treatment. Edward Thorp of Columbia University then joined the speakers for a panel discussion.

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Presented by:

This meeting is part of our Translational Medicine Initiative, sponsored by the Josiah Macy Jr. Foundation.

Academy Friend
Bristol-Myers Squibb Research and Development

Grant Support
This activity is supported by an educational donation provided by Amgen.