New treatments are needed for the 5 to 10 % of severe asthmatics who are not well controlled despite treatment with standard therapy. These severe asthmatics have persistent asthma symptoms and recurrent disease exacerbations despite treatment with high-doses of inhaled corticosteroids plus long-acting β2-agonists or oral corticosteroids. In addition, the utilization of oral corticosteroids are associated with serious and potentially debilitating side effects, such as diabetes, hypertension, weight gain, impaired host defense, reduced bone density, cataracts, skin atrophy, and myopathy. Limited alternative treatment options exist for these severe, refractory asthmatics. This project is investigating whether pharmacological agents that are in use for other disorders can be utilized for the treatment of asthma. Current studies are aimed at defining the efficacy of multi-receptor tyrosine kinase inhibitors and mTOR inhibitors for the treatment of asthma. In addition, new therapeutic approaches that are in pre-clinical development may be assessed.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$303,853
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Mishra, Amarjit; Brown, Alexandra L; Yao, Xianglan et al. (2015) Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase. Nat Commun 6:6224
Mishra, Amarjit; Yao, Xianglan; Levine, Stewart J (2013) From bedside to bench to clinic trials: identifying new treatments for severe asthma. Dis Model Mech 6:877-88
Weir, Nargues A; Levine, Stewart J (2012) Achieving symptom control in patients with moderate asthma. Clin Med Insights Circ Respir Pulm Med 6:1-11
Yao, Xianglan; Vitek, Michael P; Remaley, Alan T et al. (2012) Apolipoprotein mimetic peptides: a new approach for the treatment of asthma. Front Pharmacol 3:37
Dai, Cuilian; Yao, Xianglan; Keeran, Karen J et al. (2012) Apolipoprotein A-I attenuates ovalbumin-induced neutrophilic airway inflammation via a granulocyte colony-stimulating factor-dependent mechanism. Am J Respir Cell Mol Biol 47:186-95
Fredriksson, Karin; Fielhaber, Jill A; Lam, Jonathan K et al. (2012) Paradoxical effects of rapamycin on experimental house dust mite-induced asthma. PLoS One 7:e33984
Yao, Xianglan; Remaley, Alan T; Levine, Stewart J (2011) New kids on the block: the emerging role of apolipoproteins in the pathogenesis and treatment of asthma. Chest 140:1048-54
Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin et al. (2011) 5A, an apolipoprotein A-I mimetic peptide, attenuates the induction of house dust mite-induced asthma. J Immunol 186:576-83
Levine, Stewart J; Wenzel, Sally E (2010) Narrative review: the role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes. Ann Intern Med 152:232-7
Yao, Xianglan; Fredriksson, Karin; Yu, Zu-Xi et al. (2010) Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via a LDL Receptor-mediated Pathway. Am J Respir Crit Care Med :