Saturday, May 18, 2024
5/18/2024
Novel anti-fibrotic therapy for IPF Abstract Idiopathic pulmonary fibrosis (IPF) is characterized by myofibroblast accumulation, deposition of extracellular matrix (ECM) (including collagen and fibronectin), and progressive diffuse fibrosis in the lung interstitium. Inappropriate proliferation of fibroblasts and transformation to myofibroblasts from mesenchymal progenitor cells (MPC) play key roles in disease pathology. Although the molecular mechanisms that underlie this idiopathic disease have been obscure, recent studies implicate S100A4 as a critical autocrine-paracrine mediator of MPC self-renewal. S100A4 is both necessary and sufficient for MPCs to worsen fibrosis, making this member of the small EF-hand motif Ca2+-binding proteins a promising disease-modifying target (Xia, 2017). Recent work confirms this contention (Li, 2018). Based on these studies, during this Phase 1 project, we will generate a panel of high-affinity human monoclonal antibodies (humAbs) that block S100A4 signaling. The panel will be rank- ordered using novel in vitro assays followed by evaluation of the top candidate humAb using a novel human MPC-augmented bleomycin murine model of IPF. We are optimistic that this approach will yield a best-in-class therapy for this devastating disease.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
