A novel approach for the treatment of lung inflammatory and fibrotic diseases by increased or repaired chitinase function in lung tissues
Existing technologies for the treatment mainly target the inflammatory cells that accumulate in the tissue, but few causative agents have been identified for these severe lung diseases. This invention aims to target a ubiquitous environmentally derived xenobiotic stimulus, chitin, which causes lung inflammation and fibrosis. Chitin can be degraded by an endogenous enzyme, chitinase (acidic mammalian chitinase, AMCase, in mammals), which is dysregulated in various disease states. Previous efforts have focused on developing inhibitors of AMCase to treat other diseases such as asthma and allergy in which AMCase is overexpressed. In contrast, this invention is to increase chitinase activity, either exogenously or endogenously, to relieve and resolve the inflammatory stimulus.
Scientists at UCSF have identified distinct lung epithelial cells that secrete acidic mammalian chitinase (AMCase), an enzyme that degrades chitin. In their animal study, AMCase-deficient mice exhibit accumulation of environmentally derived chitin in the airways and develop spontaneous pulmonary fibrosis, which is ameliorated by restoration of lung chitinase activity by genetic or therapeutic approaches. In this sense, idiopathic pulmonary fibrosis (IPF) patients who accumulate excess chitin polymers in their airways can benefit from the therapeutic administration of exogenous chitinase to relieve the chitin immune stimulus.
To develop & commercialize the technology as a treatment of lung inflammatory and fibrotic diseases, and as a diagnostic to quantify amounts of chitin/chitinase or chitinase activity in lung tissues or secretions
Animal data, Under CDA/NDA
|Patent Cooperation Treaty||Published Application||WO2018191379||10/18/2018||2015-112|
Chitin, Chitinase, AMCase, Lung Inflammation, Fibrosis, Secretions, Immunology