LPA Antagonists for the Treatment of IPF

DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF) is a progressive, agonizing, debilitating and routinely fatal disease that afflicts 200,000 individuals in the United States and five million patients worldwide. There are currentlyno effective treatments available for this devastating illness. Although the etiology of IPF is currently unknown, various insults ar thought to disrupt the tight regulation between inflammation and repair of lung tissue leading to excess production of collagen by fibroblasts and the formation of excessive scar tissue, irreversibly destroying lung structure and function. The role of lysophosphatidic acid (LPA) signaling in IPF has been firmly established; through a G protein-coupled LPA1 receptor, LPA mediates recruitment of fibroblasts into the pulmonary interstitium which hyper-accelerates normal repair processes, resulting in fibrosis. A selective LPA1 receptor antagonist may intervene in the dysregulated inflammation/repair cycle, prevent fibrosis, and benefit afflicted individuals. Our long-term goal is to develop small molecule antagonists of the LPA1 receptor as potential therapeutics for IPF. The objective of this application is to identify such antagonists and evaluate them in two clinically relevantanimal models of IPF. PUBLIC HEALTH RELEVANCE: Small molecule LPA1 antagonists are potential therapeutics for idiopathic pulmonary fibrosis (IPF).