Researchers at the Icahn School of Medicine at Mount Sinai have reported early success with a new mRNA-based therapy designed to combat antibiotic-resistant infections.
The findings show that in preclinical studies using mouse and human lung tissue in the lab, the treatment slowed the growth of antibiotic-resistant bacteria, enhanced immune cell activity, and reduced lung tissue damage in a model of multidrug-resistant pneumonia.
“Our study suggests there may be new avenues to tackle antibiotic-resistant infections by supporting the immune system more directly,” said Shuchen Hou, Ph.D., lead author of the study and assistant professor of immunology and immunotherapy at Mount Sinai.
“Although we are still in the early stages and this approach has only been tested in preclinical models, these results provide an important basis for future treatments that have the potential to increase the effectiveness of traditional antibiotics.”
The growing threat of antibiotic-resistant infections
Antibiotic-resistant infections are a global threat, causing more than 1.2 million deaths each year and nearly 5 million deaths worldwide.
In the United States alone, more than 3 million infections occur annually, resulting in up to 48,000 deaths and billions of dollars in medical costs.
Experts warn that resistance is increasing in nearly every major bacterial species, putting routine surgeries, cancer treatments and newborn care at risk.
How peptibodies work to fight infections
This experimental treatment works by giving patients mRNA that instructs the body to make special infection-fighting proteins called “peptibodies.” This peptibody is designed to do two things at the site of infection. One is to directly destroy harmful bacteria, and the other is to recruit immune cells to eliminate the bacteria.
To safely deliver mRNA into patients’ bodies, the researchers packaged it into lipid nanoparticles, tiny fat-based bubbles commonly used in mRNA vaccines. These nanoparticles protect mRNA as it travels through the body and help it enter cells.
It also contains additional ingredients that reduce harmful inflammation by neutralizing excess reactive oxygen species. Reactive oxygen species are highly reactive molecules produced in the body during infections that can damage tissues and often cause severe symptoms of antibiotic-resistant infections.
Clinical tests reveal promising results
In murine models of multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, repeated doses of this therapy were well tolerated, reduced bacterial counts in the lungs, reduced inflammation, and maintained normal lung architecture.
Furthermore, similar results were obtained in clinical tests using human lung tissue, demonstrating that this therapy can be used in combination with human immune cells.
“This is the first evidence that mRNA-encoded antimicrobial peptides can directly kill bacteria while activating the immune system’s defense response,” said Dr. Dong, senior and co-corresponding author of the study and the Mount Sinai Professor of Nanomedicine.
“If future studies confirm this, it could open the door to a highly adaptable platform for developing new treatments for infections that are no longer resistant to today’s antibiotics.”
Next steps: towards human clinical trials
Next, the researchers plan to continue preclinical studies and eventually advance to human clinical trials to assess safety, dosing, and efficacy.
Although this treatment is still in its infancy, it represents an encouraging direction in the global fight against antibiotic-resistant infections.
Source link
