Abstract
Idiopathic pulmonary fibrosis (IPF) is associated with progressive destruction of the lung parenchyma with a median survival after diagnosis of three years and a five-year survival of <20%. Caveolin-1 scaffolding domain (CSD) is comprised of amino acid sequences 82-101 of the NH2 terminal region and plays a role in Caveolin-1 dimerization as well as the regulation of diverse signaling intermediates, many of which are implicated in lung fibrosis. Loss of Cav-1 protein is observed in many fibrotic diseases. Furthermore, Cav-1 deficient mice demonstrate impaired wound healing and lung morphology resembling fibrosis which is reversible with CSD peptides. LTI-03, is a seven amino acid sequence derived from the CSD domain of Cav-1. LTI-03 was efficacious in multiple mouse models of lung fibrosis (Adv-TGF-b, single bleomycin intranasal or intratracheal, and repetitive bleomycin) when delivered intraperitoneally, nebulized or as a dry powder, during the fibrotic phase of lung injury. LTI-03 treatment resulted in significantly reduced ECM proteins such as collagen in mouse lung homogenate and reduced fibrosis as measured by uCT scan and trichrome staining. Importantly, a dose dependent increase in epithelial cell survival was detected in precision cut lung slices biopsied from both non-specific interstitial pneumonia (NSIP) and end-stage IPF patients, treated with LTI-03 at physiologically relevant doses. Epithelial cell survival was measured via lysotracker staining (n=5). Furthermore, AEC2 cell markers ABCA3 and SPC were increased. LTI-03’s anti-fibrotic effects on both epithelial and fibroblasts render it a strong candidate for IPF therapy.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA1299.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019