Largest case study series ever shows success of phage therapy in more than half of patients

The number of reported cases of viruses being used to treat deadly mycobacteria infections have just increased fivefold. In a new study, a team led by researchers from the University of Pittsburgh and the University of California, San Diego reports 20 new case studies of the experimental treatment’s use, showing the therapy’s success in more than half of the patients.

This is the largest ever published set of case studies of therapy using bacteria-killing viruses known as bacteriophages, providing unprecedented detail on their use to treat serious infections while laying the groundwork for a future clinical trial.

Some of these results are dramatic, and others are complicated. But when we look at 20 cases, it becomes much more compelling that phages contribute to favorable outcomes; and in patients who have no other alternatives.”

Graham Hatfull, Eberly Family Professor of Biotechnology at the Kenneth P. Dietrich School of Arts and Sciences at the University of Pittsburgh

Each patient treated in the study was infected with one or more strains of Mycobacterium, a group of bacteria that can cause life-threatening, treatment-resistant infections in people with weakened immune systems or the lung disorder cystic fibrosis. . In 2019, Hatfull led a team showing the first successful use of phages to treat one of these infections.

“For clinicians, it’s really a nightmare: they’re not as common as other types of infections, but they’re some of the hardest to treat with antibiotics,” Hatfull said. “And especially when you take these antibiotics for long periods of time, they’re either toxic or not very well tolerated.”

Last month, University of Pittsburgh researchers participated in two new case studies successfully treating patients in collaboration with colleagues from National Jewish Health and Harvard University. But these reports represent only a fraction of the cases the team has been involved in behind the scenes. Since 2019, Hatfull and his lab have responded to requests from more than 200 clinicians seeking treatments for their patients, working with them to find phages that might be effective against the particular strain of bacteria infecting each patient.

The latest article, published today in the journal Clinical infectious diseases alongside collaborators from 20 institutions, significantly expands the body of published evidence on the therapy’s effectiveness.

“These are incredibly brave doctors, jumping off the ledge to do experimental therapy to try to help patients who have no other options,” Hatfull said. “And each of these collaborations represents a marker that can move the field forward.”

Looking at the measures of the patient’s health and whether any samples from the patient still showed signs of Mycobacterium infections, the team found that the therapy was successful in 11 out of 20 cases. No patient had an adverse reaction to treatment.

In five other patients, the results of the therapy were inconclusive and four patients showed no improvement. According to Hatfull, even these apparent failures are key to making the therapy accessible to more patients. “In some ways, these are the most interesting cases,” he said. “Understanding why they didn’t work is going to be important.”

Several unexpected trends emerged from the case studies. In 11 cases, the researchers couldn’t find more than one type of phage that could kill the patient’s infection, although common practice would be to inject a cocktail of different viruses so the bacteria are less likely to grow. a resistance.

“If you had asked me if this was a good idea three years ago, I would have had a meltdown,” Hatfull said. “But we just didn’t see any resistance, and we didn’t see any treatment failure due to resistance, even using just one phage.”

Additionally, the team found that some patients’ immune systems attacked the viruses, but only in a few cases did their immune systems render the virus ineffective. And in some cases, the treatment was still successful despite such an immune reaction. The study paints an encouraging picture for therapy, Hatfull said, and one that opens up the possibility of new phage regimens that clinicians could use to maximize the chances of treatment success.

Besides the importance of the study for patients dealing with Mycobacterium infections, it also represents a substantial advance for the broader field of phage therapy. A concern in some corners is that researchers only publish case studies in which phage therapy is successful.

“A series of back-to-back case studies, where we don’t select, is a much more transparent way to see what works and what doesn’t,” Hatfull said. “It adds considerable weight to the feeling that the therapy is safe.”

The lab continues to provide phage to more patients -; while conducting research to expand the funnel that reduced an initial group of 200 patients to 20, in hopes of providing treatment to more people with no other option.

“We haven’t yet figured out how to find or engineer phages that can catch all strains of bacteria in these patients,” Hatfull said. “This represents one of the main challenges ahead.”