Related Experiment Video
Updated: Mar 25, 2026
Development of Obliterative Bronchiolitis in a Murine Model of Orthotopic Lung Transplantation
Published on: July 10, 2012
The Selective JAK1/3-Inhibitor R507 Mitigates Obliterative Airway Disease Both With Systemic Administration and
Tobias Deuse1, Xiaoqin Hua, Mandy Stubbendorff
11 TSI Laboratory, University Heart Center Hamburg, Hamburg, Germany. 2 Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Hamburg, Germany. 3 Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany. 4 Department of Surgery, TSI Laboratory, University of California San Francsico (UCSF), San Francsico, CA. 5 Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford, CA. 6 Department of Anaesthesiology, University Hospital Hamburg, Hamburg, Germany. 7 Rigel Pharmaceuticals, South San Francisco, CA. 8 Aerogen Ltd, Galway, Ireland. 9 Department of Clinical Chemistry, University Medical Center Hamburg, Hamburg, Germany. 10 Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. 11Department of Cardiothoracic Surgery, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.
The Janus kinase 1/3 inhibitor R507 effectively prevented airway obliteration in transplantation models. This well-tolerated immunosuppressant showed efficacy via both oral and inhaled routes, preserving airway epithelium.
Area of Science:
- Immunology
- Transplantation Biology
- Pharmacology
Background:
- Obliterative airway disease is a significant complication following airway transplantation.
- Current immunosuppressive strategies have limitations in preventing this outcome.
Purpose of the Study:
- To evaluate the efficacy of R507, a selective Janus kinase 1/3 inhibitor, in preventing obliterative airway disease.
- To assess the safety and anti-inflammatory effects of R507 in preclinical airway transplantation models.
Main Methods:
- Orthotopic trachea transplantations were performed in a rat model.
- Immunosuppression was achieved using oral everolimus or oral/inhaled R507.
- Graft analysis, toxicity studies on human airway epithelial cells, and assessment of immune activation were conducted.
Main Results:
- R507 significantly reduced mononuclear cell infiltration and preserved respiratory epithelium compared to everolimus.
- Both oral and inhaled R507 were highly effective in preventing airway obliteration over 60 days.
- R507 demonstrated a favorable safety profile, with no observed airway toxicity and no adverse effects on kidney function or lipid profiles, unlike everolimus.
Conclusions:
- R507 is a well-tolerated immunosuppressant effective in preventing obliterative airway disease.
- Both systemic and inhaled administration of R507 show comparable efficacy in preclinical models.
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