Researchers at the University of California, Irvine have developed a new peptide that has been found to effectively suppress the lung inflammation associated with Acute Respiratory Distress Syndrome (ARDS). This study, which appears in the journal iScience, describes the first specific treatment designed to prevent the deadly disease, which can appear in patients with severe lung injury from infections with bacteria and viruses, such as pneumonia, flu, respiratory syncytial virus (RSV), and COVID-19. The C6 peptide works by blocking voltage-gated Hv1 proton channels in white blood cells called neutrophils, which suppresses the production of harmful reactive oxygen species, proteases, and cytokines, and prevents infiltration of the lung tissue by these cells that trigger uncontrolled inflammation and fluid buildup seen in severely damaged lungs.
The research team behind this study was headed by Dr. Steven A.N. Goldstein, a distinguished professor of pediatrics, psychiatry & biophysics and pharmaceutical sciences at UC Irvine, as well as Ruiming Zhao, an assistant project scientist at UC Irvine and Dr. Andreas Schwingshackl, an associate professor of pediatrics at UCLA.
Acute Respiratory Distress Syndrome (ARDS) is a condition characterized by inflammation and fluid buildup in the lungs, which can be caused by injury or infection. This inflammation and fluid buildup damages the lung tissue, reducing the amount of oxygen that can reach the bloodstream. Symptoms of ARDS include severe shortness of breath and oxygenation failure, often requiring support from a ventilator.
According to several studies conducted over the past decade, ARDS affects around 200,000 adults and 8,000 children in the United States each year. This results in 75,000 deaths among adults and 1,500 deaths among children. Survivors of ARDS often experience long-lasting negative effects, such as cognitive dysfunction, mental health issues, and physical impairments, with only 50% of ARDS patients discharged from the hospital returning to their jobs within the first two years.
In a mouse model of the disease, the researchers administered the C6 peptide in a clinically relevant manner to suppress the disease. They also found that C6 suppresses Hv1 in human neutrophils, which are the primary inflammatory cells that accumulate in the lungs of ARDS patients, by shutting down the same inflammatory pathways that it does in mice. The absence of any toxic side effects observed in the mice suggests that targeting Hv1 will be well-tolerated in humans as a therapeutic approach for ARDS and that C6 may also be useful in treating other inflammatory diseases.
The C6 peptide was first created by the UC Irvine researchers in 2018, and they found that it could be made more potent by linking two peptides together in 2022. Peptides are small chains of amino acids and are becoming more commonly used as drugs in recent years. They are a subset of medications called biologics that are proving desirable for drug discovery. They differ from proteins like antibodies, which are made from longer and more complex amino acid chains.
The next steps for the research team include further study of C6, its derivatives, and small molecule mimetics that they have isolated to treat inflammatory diseases of the lungs and other tissues, including assessment of how long the peptide stays in the body and how it is eliminated.