Locus’ therapy is actually a cocktail of six phages. The company used artificial intelligence to predict a combination that would be effective against E. coliThree of the phages are “lytic,” meaning they work by infecting E. coli The cells burst open and burst open. The other three are engineered to contain Crispr to enhance their effectiveness. Once inside the target cells, these phages use the Crispr system to target a crucial site on the E. coli genome and begin to degrade the bacteria’s DNA.
Some phages are very good at entering bacterial cells, but not at killing them. “That’s where gene editing comes in,” explains Paul Garofolo, Locus’s chief executive. He says the therapy is designed to “go into the human body and eliminate a specific bacterial species without touching anything else.”
In a phase 2 trial, 16 women received a three-day treatment with the phage cocktail, along with Bactrim, an antibiotic commonly prescribed for urinary tract infections. Within four hours of the first treatment, levels of the phage cocktail E. coli in urine decreased rapidly and were maintained until the end of the 10-day study period. At that time, UTI symptoms in all participants had disappeared and levels of E. coli were low enough in 14 of 16 women to be considered cured.
The findings were reported on August 9 in The diary The Lancet Infectious DiseasesThe Biomedical Advanced Research and Development Authority, or BARDA, part of the U.S. Department of Health and Human Services, is co-developing the therapy.
Urinary tract infections are incredibly common and about half of all women will have a UTI at some point in their lives. More than 80 percent of infections are caused by E. coliand in a Report 2022, The World Health Organization found that one in five urinary tract infections are caused by E. coli They showed reduced susceptibility to standard antibiotics such as ampicillin, cotrimoxazole and fluoroquinolones.
While phage therapy is common in the Republic of Georgia and Poland, it is not licensed in the US. However, it is used experimentally in certain cases with permission from the US Food and Drug Administration. A major challenge with commercializing phage therapy is that it is often customized to individual patients and therefore difficult to scale. Finding the right phage for treatment can take time, and batches of phages then need to be grown and purified. But using a fixed cocktail like Locus’s would mean the therapy could be scaled more easily.
And there’s another potential benefit. “Crispr-enhanced phages allow for degradation of the bacterial genome and would bypass several mechanisms by which bacteria can become resistant to phages,” says Saima Aslam, a professor of medicine at the University of California, San Diego, who studies phages but is not involved in developing Locus therapy. “In theory, this can prevent the regrowth of phage-resistant bacteria and thus lead to a more effective treatment.”
Photo: Locus Biosciences
