A pioneering therapy that attacks the Achilles heel of a common and deadly bug may be a promising treatment for multidrug-resistant infections, suggests preliminary research.
The new therapy, a monoclonal antibody, appears to be very effective in treating a strain of Pseudomonas aeruginosa resistant to 19 of 21 drugs available to treat it, according to a study being presented at the 49th annual meeting of the Infectious Diseases Society of America (IDSA). Pneumonia caused by Pseudomonas aeruginosa is a serious problem in hospitals.
Monoclonal antibody therapy, which uses laboratory-created proteins to attack a specific part of a targeted cell, is a growing and prominent treatment for cancer and inflammatory disorders. Monoclonal antibodies imitate antibodies that the body’s immune system naturally produces to fight illness, which is why researchers believe it is so effective.
While traditional antibiotics typically target the ability of bacteria to replicate, the monoclonal antibody being tested in the study disables the bacterium’s tail (called the flagellum), an appendage that propels it throughout the body, helping it to spread, adhere and ultimately infect cells.
“The flagellum is an important weapon for bacteria, but we’ve found it is vulnerable to this monoclonal antibody, which disables it, interfering with the bacterium’s ability to move. That gives the immune system a head start in trying to combat the infection,” says Lewis Neville, PhD, founder and CEO of Lostam BioPharmaceuticals, part of the New Generation Technology (NGT) incubator in Nazareth, Israel. “Also, research shows that bacteria are unlikely to mutate by shedding the all-important tail, meaning they are less likely to develop resistance to this type of therapy.”
In the study, researchers infected mice with a multidrug-resistant strain of Pseudomonas aeruginosa pneumonia and one hour later injected 20 mice each with the mouse version of the monoclonal antibody, the human version of the monoclonal antibody and imipenem, the antibiotic commonly used to treat these types of infections. After seven days, 75 percent of mice that received mouse monoclonal antibody, 60 percent that received human monoclonal antibody, and 30 percent that received imipenem had survived. Researchers gave a second dose of the human monoclonal antibody 24 hours later to another group of 20 mice, and 75 percent were alive after seven days, suggesting two doses provides more benefit, says Neville.
Testing in humans is a few years away, but if successful, the monoclonal antibody therapy could be a very promising treatment for Pseudomonas aeruginosa pneumonia. The infection is a scourge in hospitals, particularly in ventilated patients and those with cystic fibrosis, half of whom are permanently colonized with Pseudomonas aeruginosa, and many of whom die of the infection.
The next step is to test the ability of the monoclonal antibody to treat other infections caused by Pseudomonas aeruginosa, such as urinary tract infections and blood stream infections, according to Neville.
“We desperately need new methods to treat these difficult highly resistant infections and a drug that successfully takes a different approach is welcome news,” says Thomas G. Slama, MD, IDSA president-elect and clinical professor of medicine at Indiana University School of Medicine, Indianapolis. “If they prove effective, new therapies such as these could be used alone or in combination with other antibiotics to provide more options for treatment.”