Novel Protein and Lipid Therapeutic Targets for Exacerbation-Prone Asthma

Asthma causes difficulty breathing, coughing, and shortness of breath in about 25 million Americans, costing the US at least $80 billion annually and resulting in more than 1.5 million visits to the emergency department, half a million hospitalizations, and 3500 deaths each year. During an asthma attack, or exacerbation, affected individuals have only two possible effective treatments: corticosteroids or beta-adrenergic agents. Neither are uniformly effective or address the underlying cause of the exacerbation. Patients quickly develop a tolerance to beta adrenergic drugs, while corticosteroids are slow to act. Preventing an exacerbation is only possible through daily inhaled corticosteroids where adherence is poor or very expensive antibody therapies, which also cannot treat asthma exacerbations.

Description

Researchers have identified novel protein and lipid therapeutic targets for exacerbation-prone asthma with the potential to both prevent and reduce the severity of asthma exacerbations. Worsening oxidative stress causes overwhelm of protective enzymes and drives ferroptic cell death. This oxidative stress-induced cell death disrupts epithelial barriers and promotes asthma exacerbation. Blocking ferroptosis at these targets using small molecule inhibitors offers a novel approach to both preventing and treating asthma exacerbations, improving quality of life and reducing morbidity and mortality for millions of affected individuals.

Applications

· Current therapies are not uniformly effective
· Treats the underlying cause of asthma exacerbations
· Work immediately, compared to corticosteroids that can take hours or days to be treat exacerbations (?)
· Prevents tachyphylaxis and development of drug tolerance (?)
· Less expensive than costly biologic antibody therapies (?)

Advantages

· Preventing and treating asthma attacks

Invention Readiness

In vitro data

IP Status

https://patents.google.com/patent/US20240002350A1

Related Publication(s)

Wenzel, S. E., Tyurina, Y. Y., Zhao, J., St. Croix, C. M., Dar, H. H., Mao, G., Tyurin, V. A., Anthonymuthu, T. S., Kapralov, A. A., Amoscato, A. A., Mikulska-Ruminska, K., Shrivastava, I. H., Kenny, E. M., Yang, Q., Rosenbaum, J. C., Sparvero, L. J., Emlet, D. R., Wen, X., Minami, Y., … Kagan, V. E. (2017). PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell, 171(3), 628-641.e26. https://doi.org/10.1016/j.cell.2017.09.044