TrialLineage Concept
Lysophosphatidic acid signaling
Lysophosphatidic acid (LPA) is a bioactive lipid that acts as a signaling molecule through specific cell-surface receptors. In fibrotic disease, LPA signaling promotes fibroblast activation, migration, and survival — making it a target for antifibrotic drug development.
What is LPA signaling?
LPA is one of the simplest phospholipids in biological membranes. For decades it was considered merely a metabolic intermediate in lipid synthesis. Research in the 1990s and 2000s revealed that LPA is a potent extracellular signaling molecule, released from activated platelets, injured cells, and other sources.
LPA signals through a family of at least six G protein-coupled receptors (LPA1 through LPA6). Through these receptors, LPA regulates cell proliferation, migration, survival, and cytoskeletal organization. LPA levels are elevated in injured and fibrotic tissues, including the lungs of patients with IPF.
Connection to the IPF lineage
The discovery that LPA is elevated in fibrotic lungs and drives fibroblast behavior through specific receptors is what made LPA receptor antagonism a rational antifibrotic strategy. Without the identification of LPA as a profibrotic mediator, the BMS-986278 trial would not exist.