Identification of Novel Compounds to Treat Airway Smooth Muscle Dysfunction
- 詳細技術說明
- Given the lack of viable lung disease treatments, researchers at the University of Iowa funded by the American Asthma Foundation and Cystic Fibrosis Foundation recognize an opportunity to discover new drugs for chronic lung diseases that (1) improve the quality of patient life (2) prevent the underlying symptoms of disease (3) lack unwanted side effects.
- *Abstract
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Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function causes cystic fibrosis (CF). Airway smooth muscle lacking CFTR has an abnormal contractile phenotype. We used laser capture microdissection to isolate RNA from airway smooth muscle in newborn pigs (non-CF and CF pigs). We then performed RNAseq on this tissue and looked at the differentially expressed genes in CF vs. non-CF. We then ran this expression profile through the LINCS database and identified a list of compunds predicted to reverse the abnormal transcript profile in CF airway smooth muscle. Thus far, we have tested NVP-TAE684 [an inhibitor of anaplastic lymphoma kinase (ALK - Selleckchem]. When we pretreat airways with this compound it significantly reduces airway narrowing, suggesting it might have a role in CF or other diseases of airway narrowing such as asthma. Ceritinib, a "cousin" of this compound, is FDA approved for the treatment of metastatic non-small cell lung cancer.
- *Licensing
- Email: uirf-marketing@uiowa.eduPhone: (319) 335-4546
- 國家/地區
- 美國
