Novel Glycan Therapeutic to Treat ARDS
Abstract
Problem: Acute Respiratory Distress Syndrome (ARDS) is a lung injury that can result from traumatic injuries or infections (including COVID-19 infection). The mortality rate in patients who develop ARDS is extremely high at approximately 40%. No drug therapies are available and treatment for ARDS is only supportive (oxygen, body positioning, and mechanical ventilation, for example). Soldiers living in close quarters and in combat are at higher risk for infections or injuries that lead to ARDS, while Veterans, families of military personnel, and civilians also develop ARDS. The current COVID-19 pandemic highlights the need for ARDS treatment for both military personnel and civilians. We therefore propose to identify a new therapeutic that can treat ARDS and save lives. This proposal thus addresses FY21 Topic Area Respiratory Health Area of Encouragement 1: Development and/or testing of novel and/or innovative treatments to prevent or delay the progression of acute lung injury (ALI)/ARDS. Innovation: We propose to identify a new molecule that would be the first drug therapy to treat ARDS. An overactive inflammatory response is believed to underlie the organ failure that develops in patients with ARDS. Neutrophils are one of the first inflammatory cells that respond to injury and are a main driver of this excessive inflammation that damages the lung and other organs in ARDS. Reducing the neutrophil response is thus a promising approach for ARDS treatment. We identified a drug class, called glycans, which are a type of large sugar molecules that have a wide range of anti-inflammatory activity. For example, glycans can selectively reduce the neutrophil response in ARDS without completely shutting down the body’s natural and healthy immune response. The most common glycan drug is heparin, which is a blood thinner and is used to treat or prevent blood clots. Heparin has strong anti-inflammatory properties, but its use as an anti-inflammatory drug is limited because it puts patients at risk for bleeding. We modified heparin so that it does not cause bleeding but retains its critical anti-inflammatory properties. We propose to identify the most promising of our glycan molecules by testing the anti-inflammatory properties in laboratory bench tests and in animal models that mimic ARDS in humans. Impact: Our research could lead to a new drug that can treat ARDS and save lives. We will also learn important mechanisms for controlling the detrimental inflammatory response, which could help inform other innovative approaches to treat ARDS. With such a high death rate and very limited options for treating ARDS, a positive outcome from our research could save the lives and reduce disability in Soldiers and civilians who are afflicted with ARDS. It is noteworthy that ARDS often afflicts young otherwise healthy Soldiers and civilians and causes considerable highly detrimental economic and social consequences that could also be avoided if an effective treatment was discovered. Our research could provide the new information needed to justify and guide testing and obtain additional funding to evaluate our new anti-inflammatory molecule in clinical trials of patients with ARDS.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210093
Entities
People
- John Paderi
Organizations
- United States Army