Locus’s therapy is actually a cocktail of six phages. The company used artificial intelligence to predict which combination would be effective against E. coliThree of the phages are “lytic,” meaning they work by infecting E. coli cells and causing them to burst. The remaining three are designed to contain Crispr to escalate their effectiveness. Once inside the target cells, these phages employ the Crispr system to lock onto a key site in E. coli genome and start degrading the bacterial DNA.
Some phages are really good at getting into bacterial cells, but they’re not very good at killing them. “That’s where gene editing comes in,” explains Paul Garofolo, CEO of Locus. He says the therapy is designed to “get into the human body and eliminate the target bacterial species without touching anything else.”
In a phase 2 study, 16 women were given a phage cocktail for three days along with Bactrim, a commonly prescribed antibiotic for UTIs. Within four hours of the first dose, the level E. coli in urine decreased rapidly and remained until the end of the 10-day study period. By that time, UTI symptoms had resolved in all participants, and levels E. coli In 14 of the 16 women, the results were low enough to be considered cured.
The results were published on August 9 in journal 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 extremely common, and about half of women will have a urinary tract infection in their lifetime. More than 80 percent of infections are caused by E. coliand in Report 2022The World Health Organization has determined that one in five urinary tract infections is caused E. coli showed reduced susceptibility to standard antibiotics such as ampicillin, co-trimoxazole and fluoroquinolones.
Although phage therapy is common in the Republic of Georgia and Poland, it is not licensed in the U.S. It is, however, being used experimentally in some cases with U.S. Food and Drug Administration approval. A major challenge with commercializing phage therapy is that it is often tailored to individual patients and therefore hard to scale up. Finding the right phage for a treatment can take time, and batches of phage must then be grown and purified. However, using a fixed cocktail like Locus would mean that the therapy could be more easily scaled up.
And there’s another potential benefit. “Crispr-enhanced phages enable 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. “Theoretically, this could prevent the regrowth of phage-resistant bacteria, leading to more effective treatments.”
Photo: Locus Biosciences