World-first human treatment of antibiotic-resistant infection with genetically modified virus
A new case study, described in the journal Nature Communications, outlines the world's first use of a genetically modified virus to treat a life-threatening antibiotic-resistant bacterial infection. The successful treatment paves the way for larger clinical trials to try to establish how broadly effective this experimental process could be in wider patient populations.
A bacteriophage, commonly referred to as a phage, is a type of virus known to attack and kill bacteria. For over a century scientists have investigated these viral agents for their antibacterial activity, but research stalled following the discovery of antibiotics. More recently, as the threat of antibiotic resistant bacteria grows, scientists have rediscovered the potential of phages.
For several decades molecular geneticist Graham Hatfull, from the Howard Hughes Medical Institute at the University of Pittsburgh, has been amassing a collection of phages from locations all over the globe. The project, called SEA-PHAGES, was ostensibly geared toward building a straightforward library of biological data, however all that changed in late 2017 after Hatfull was contacted by a colleague in London.
"I had a sense that this collection was enormously powerful for addressing all sorts of questions in biology," says Hatfull. "But we didn't think we'd ever get to a point of using these phages therapeutically."
Two young patients with cystic fibrosis were suffering major antibiotic-resistant bacterial infections following lung transplant surgery. Doctors contacted Hatfull in the hopes he could track down a phage in his large collection with a taste for the particular bacterial strain targeting the young patients.
Several months after receiving samples of the bacteria, Hatfull's team found a phage that effectively targeted one of the patients' bacterial infections. Unfortunately, it was too late, with that first patient dying just weeks earlier from the infection.
Moving focus to the other patient's bacterial strain, the team homed in on three potential phages. To increase their bacterial killing efficiency, two of the phages were genetically modified and then the three viruses were combined into a cocktail containing a billion phage particles per dose.
The subsequent treatment was incredibly successful, albeit somewhat onerous. The patient spent the next six months receiving twice-daily intravenous infusions alongside topical treatments for her skin lesions. Six weeks after starting the treatment, a scan of the patient's liver showed the infection has almost completely disappeared. The superficial infections across the patient's body responded to the treatment much more slowly. To date, all but one of the patient's skin infections have cleared.
These incredibly promising results suggest a bright future for phage treatments. However there are significant challenges to overcome before more widespread clinical uses can be rolled out. Perhaps the biggest hurdle is the personalized nature of the therapy. This particular case took a team of researchers months to produce a treatment specifically tailored for a single patient. It is unclear how easy it would be to develop a kind of broad spectrum phage cocktail that can target bacterial infections more generally.
It is also important to note this is an isolated case study and not a larger clinical trial. So there is no certainty that the phage treatment was the direct cause of the patient's recovery, or whether the treatment will generally work for other patients. On the bright side, the side effects to the treatment were almost nonexistent, and the researchers report that the bacteria is showing no sign of developing a resistance to the phage attack.
The case study is outlined in an article published in the journal Nature Communications.
Source: Howard Hughes Medical Institute