Therapeutic for viral infection-triggered asthma with c-Kit inhibitor
Inventors: Dale Umetsu, Rosemarie DeKruyff, Ya-Jen Chang, Dale Umetsu, Nicole Baumgarth
Invention Types: Therapeutics
Research Areas: Allergy/Respiratory/Pulmonary Disease, Immunology
Keywords: For More Information Contact: Meyer, Abbie
There are currently over 25 million individuals with asthma in the United States. Viral infections may trigger or exacerbate asthma, and represent a significant cause of morbidity. It is estimated that up to 80% of acute asthma exacerbations are the result of viral infections. Inhaled and systemic corticosteroids are effective for allergic asthma, but there is no current standard of care for viral-induced asthma, which results in high rates of hospitalization.
Researchers in the Umetsu lab at Boston Children’s Hospital have discovered the role of a new innate lymphoid cell type, termed natural helper cell or nuocyte, in the lungs of an experimental mouse model. They demonstrated that viral-mediated induction of airway hyper-reactivity (AHR), a defining feature of asthma, was mediated by IL-33, its receptor ST2 and natural helper cells, which express the stem cell growth factor receptor c-Kit. In their research, the use of a c-Kit kinase inhibitor was shown to greatly limit influenza-induced AHR in vivo and suppress the activity of natural helper cells in vitro. In particular, they demonstrated a dose-dependent inhibition of nuocyte proliferation and reduced secretion of IL-5 and IL-13, known mediators of asthma pathogenesis.
• C-Kit inhibitors as therapeutics for viral-induced asthma by prevention of airway hyper-reactivity and inflammation
• c-Kit inhibitors may serve as a viable treatment option for children, who are more susceptible to viral infections
• c-Kit inhibitors mediate a pathway independent of Th2 cells and adaptive immunity
• Long-term treatment with c-Kit inhibitors is associated with few side effects. Treatment of viral-induced asthma should only require short-term doses, decreasing the risk of side effects
Chang YJ, Kim HY, Albacker LA, et al. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nature Immunology 2011 May 29;12: 631-638.
Kim HY, Chang YJ, Subramanian S, et al. Innate lymphoid cells responding to IL-33 mediate airway-hyperreactivity independent of adaptive immunity. J Allergy Clin Immunol. 2012 Jan; 129(1): 216-27.
IPStatus: Pat. Pend.