Israeli scientists are working to develop a “precision weapon” against intestinal diseases consisting of viruses that fight bacteria.
Two different viral “cocktails” have undergone phase 1 clinical trials, with initial results suggesting they are safe and extensive in vitro and animal testing suggesting they fight bacteria.
Peer-reviewed research published in the journal Cell says the virus was effective in reducing the numbers of Klebsiella pneumoniae, a bacterium found in large amounts in the gut of people with Crohn’s disease and ulcerative colitis.
“To our knowledge, this represents the first ‘silver bullet’ approach that promises precise suppression of disease-causing gut microbes without damaging the surrounding microbiome,” said Prof. Eran Elinav of the Weizmann Institute of Science, who led the research team.
The idea of using viruses in drugs to fight bacteria – known as bacteriophages or phage therapy – is not new and was extensively researched in the early 20th century. Before significant gains were made, however, antibiotics were invented and attempts to use viruses clinically were largely abandoned—although scientists continued to use phages in laboratory settings.
Today, there is a resurgence of interest in potential phage therapies amid concerns about antibiotic-resistant bacteria. Some researchers have suggested they may provide a solution to the problem, and several phage therapies are in development, although none are widely used.
Weizmann Institute of Science researchers (left to right) Dr. Rafael Valdes Mas, Dr. Sara Federici, Prof. Eran Elinav and Dr. Denise Kviatcovsky (courtesy Weizmann Institute of Science)
The Weizmann Project began with scientists analyzing the microbiome of people with Crohn’s disease and ulcerative colitis to find out which bacteria it would be helpful to fight against.
dr Sara Federici, a member of the research team, told The Times of Israel: “We looked at four different cohorts of people and found a bacterium in people with Crohn’s disease and ulcerative colitis, Klebsiella pneumoniae, and decided to attack it with bacterial phages which are neither cells harm other bacteria. So with super-specific bacteria.”
Federici said the team “identified viruses — or phages — that had the potential to fight the bacteria and tested them against the bacteria in vitro and then in mice with Crohn’s disease and ulcerative colitis.” From these results, she said: “We could see which of the viruses were the most effective. We then selected the best viruses and tested them on a laboratory device that mimics a human gut and got good results.”
In the latest development, two combinations of viruses — or “cocktails” — were treated in a phase 1 clinical trial. “The study participants took the phage for six days and there were no side effects,” said Federici. The phages persisted in the human gut and even multiplied over time while not causing any unwanted changes in the rest of the gut microbes, she added.
The phages will now undergo further clinical testing to see if they fight bacteria and benefit health in a real-world setting.
The Weizmann researchers hope to develop them into drugs that will either treat Crohn’s disease and ulcerative colitis, or potentially stave off the diseases in people with high levels of Klebsiella pneumoniae.
“Our vision is to eventually develop personalized therapies for a variety of diseases,” Elinav said, “where the disease-causing gut bacterial strains are identified in each patient and a phage cocktail is engineered to kill only those strains.”
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