UVM Reference Number: C469
Summary:
Inhalable and lung-specific treatments to prevent and repair restructuring in fibrotic lung tissue
Background:
Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease for which no effective treatments are available. Current treatment options, pirfenidone and nintedanib have substantial side-effects and do not extend survival. IPF is a disease that is accompanied by oxidative stress, however, generic non-specific antioxidants, such as N-acetyl-cysteine, are not effective
Technology Overview:
The redox systems group at the Vermont Lung Center has identified a new model for epithelial cell control of lung fibrosis, asthma, and lung cancer via modulation of certain redox homeostasis mechanisms. As published in Nature Medicine 2018, a specific type of protein oxidation, S-glutathionylation, is increased in lungs from patients with IPF and glutaredoxin (GLRX), a highly potent catalyst, was inactivated. Using multiple pre-clinical mouse models, it was found that absence of GLRX greatly sensitizes mice to development of fibrosis, protein S-glutathionylation can be reversed by GLRX, and transgenic overexpression of GLRX protects from fibrogenesis. In addition, direct administration of recombinant GLRX into airways reversed existing increases in fibrosis.
GLRX is now being developed as an inhaled biologic for the treatment of fibrosis and initial work has been done towards preparation for clinical studies. In addition, 2 targets beyond GRX1 were identified that also regulate this redox homeostasis: GSTP and PDIA3. More recent work on the role of PDIA3 in chronic asthma and on GSTP’s glycolysis regulation role in KRAS positive lung cancer cells, make this system an attractive new therapeutic paradigm for several debilitating lung diseases.
Further Details:
- Reducing protein oxidation reverses lung fibrosis Anathy et al PMID29988126
- Dysregulation of the glutaredoxin/S- glutathionylation redox axis in lung diseases Chia et alPMID31693398
Benefits:
- Novel therapeutic targets that regulate lung oxidation damage
- Can prevent and repair restructuring in fibrotic lung tissue
- Inhalable and lung specific treatments
Applications:
- Treatment and repair of fibrotic lung diseases
- Idiopathic pulmonary fibrosis, lung cancer, asthma
Opportunity:
- Licensing and collaborations for GRX and small-molecule inhibitor development
Patents:
- US Patents: 8,679,811B2; 9,907,828B2; 10,688,150B2
- US Non-Provisional Application US20200276263A1
Seeking:
- Licensing
- Development partner
