Arf6 Inhibitor for Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome
Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) can result from several causes, including but not limited to, pulmonary aspiration, severe lung infections, smoke or chemical inhalation, direct trauma to the chest, fat emboli, or multiple transfusions. There are an estimated 190,000 cases of ALI/ARDS each year in the US, and ARDS is a major complication and cause of death with SARS-Cov-2 infection. Many chemical and biological weapons cause ALI/ARDS, and so the absence of an effective therapy makes Warfighters and the general population extremely vulnerable to such attacks. Some degree of ARDS occurs in between 26-33% of combat casualties. Mortality rates in patients with ALI/ARDS remain at approximately 40% even with current advances in critical care. Management of ALI/ARDS is challenging because care is limited to supportive measures, which are often inadequate. These measures consist of mechanical ventilation, fluid management, and, where possible, treatment of the underlying cause. There are no specific pharmacotherapies for prevention or treatment of ARDS. Our small-molecule ARF6 inhibitor, A6-5188, is pathogen-agnostic in that it reduces vascular permeability induced by several inflammatory cytokines and growth factors as well as several bacterial infections, both Gram-negative and Gram-positive. We envision that A6-5188 will be used as first-line therapy for patients with ARDS or at risk of developing ARDS regardless of the causative agent(s), and adjunctive to targeted antibacterial therapy initiated subsequent to pathogen identification. This grant is focused on nonclinical development of A6-5188 through IND filing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2021
- Accession Number
- AD1148566
Entities
People
- Alan L Mueller