ARF6 Inhibitor for Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome
Abstract
Background: 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. 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. There are no specific drugs for prevention or treatment of ARDS. This proposal addresses the Topic Area of Acute Lung Injury. Further, this proposal addresses an Area of Encouragement for Acute Lung Injury, namely, novel and/or innovative detection technologies or therapeutics to reduce the incidence and/or severity of ALI/ARDS and/or other lung injury secondary to trauma, transfusion, infection, burns, hemorrhagic shock, inhalation, and/or oxygen exposure. Proposed Research: ARDS is characterized by inappropriate leak of fluid from the bloodstream into surrounding tissues and organs (“vascular leak”). Accumulation of fluid within the lungs leads to poor oxygen exchange such that patients require supplemental oxygen. Navigen has discovered a first-in-class drug, A6-5188, which minimizes the degree of vascular leak seen in animal models following lung injury or infection. While A6-5188 itself does not treat the underlying cause of the lung injury, by blocking vascular leak, it could be used to improve blood oxygenation and improve patient outcome, including survival, while giving the physician time to better treat the underlying infection or injury. It is also important that A6-5188 does not suppress the body’s immune system, so the immune system can continue its work to fight and clear an infection. In addition, A6-5188 minimizes vascular leak no matter what the cause, e.g., injury or infection, so that a patient with lung injury or at risk of developing lung injury could start treatment with A6-5188 while the underlying cause is being investigated. Impact: Work carried out under this proposal will be to manufacture A6-5188 drug and evaluate the safety of A6-5188 in animal studies that are required by the Food and Drug Administration (FDA) prior to performing clinical trials in people. After completion of these studies, we will file an Investigational New Drug (IND) application with the FDA. Once our IND is accepted by the FDA, we can begin trials in healthy volunteers to explore the safety of A6-5188 in humans and study how the drug is handled (metabolized and excreted). To summarize, A6-5188 has the potential to be a first-in-class drug used as first-line therapy for patients with ARDS or at risk of developing ARDS regardless of the cause(s).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010239
Entities
People
- Alan Mueller
Organizations
- Navigen (United States)
- United States Army