Use of tight junction antagonists in the treatment of acute lung injury and acute respiratory distress

Abstract

The present application provides compositions and methods for treating acute lung injury and acute respiratory distress syndrome. The methods include administering one or more tight junction antagonists to the lung of a subject in need thereof.

Description

BACKGROUND[0001]Acute Respiratory Distress Syndrome (ARDS) presents in about 150,000 individuals in the US annually, with a mortality rate of 30-50%. ARDS occurs in response to diverse forms of severe injury, in which lung edema results in respiratory failure. The current standard of care for ARDS is limited to the management of the disease through supportive mechanical ventilation. The loss of endothelial barrier integrity is central to the pulmonary edema that occurs in ARDS.[0002]Triggering causes for Acute Lung Injury (ALI) including ARDS can, for example, be diffuse pulmonary infections (e.g. due to viruses, bacteria, fungi), aspiration of liquids (e.g. gastric juice or water), inhalation of toxins or irritants (e.g. chlorine gas, nitrogen oxides, smoke), direct or indirect trauma (e.g. multiple fractures or pulmonary contusion), systemic reactions to inflammations outside the lung (e.g. hemorrhagic pancreatitis, gram-negative septicemia), transfusions of high blood volumes or ...

AI Technical Summary

Benefits of technology

The present invention provides methods for treating lung tissue with tight junctions that have an excessive or undesirable permeability. The methods may involve administering a composition containing a tight junction antagonist, such as a peptide (e.g. SEQ ID NOs:1-24 or G-G-V-L-V-Q-P-G (SEQ ID NO: 15)). The tight junction antagonist may be used alone or in combination with other components such as aminosalicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines, and biologic therapeutics. The compositions may be formulated for pulmonary delivery. The technical effect of this invention is to provide new methods and compositions for treating lung tissue with tight junctions that have an excessive or undesirable permeability.

Problems solved by technology

ARDS occurs in response to diverse forms of severe injury, in which lung edema results in respiratory failure.

The current standard of care for ARDS is limited to the management of the disease through supportive mechanical ventilation.

Loss of this endothelial barrier integrity is the central defect found in ALI and ARDS.

Images