Probiotic engineered to clear ammonia from the body passes first phase of human trials
As we learn more and more about how the bacteria in our gut can affect our entire body, some researchers are looking to specifically genetically engineer probiotics to act as novel, living medicines. New data published in the journal Science Translational Medicine has described the results of a human trial testing the safety of a non-pathogenic strain of E. coli engineered to mop up excess ammonia in a person's large intestine.
Ammonia is naturally produced in the human body, generally as a byproduct when we metabolize proteins. It is commonly considered a waste product and filtered out of our body by the liver and kidneys, but sometimes, due to defects in detoxification processes, or overproduction, excessive levels of ammonia can build up. This condition is called hyperammonemia.
We know that one strain of bacteria in our gut, called E. coli nissle, can effectively convert ammonia into another safer molecule called arginine. Scientists hypothesized that this specific strain of bacteria could be engineered to overproduce arginine, thus becoming a much more effective sponge for excess ammonia in the human body.
Preclinical studies demonstrated the engineered bacteria, dubbed SYNB1020, to be effective in reducing ammonia levels in animal models of hyperammonemia. Of course, animal experiments may be successful, but actually testing genetically engineered bacteria in human beings is a whole different story.
Excitingly, the first Phase 1 human trial results for SYNB1020 have just been published and they suggest the bacteria to be both safe and effective. No significant side effects were seen in the 52 healthy volunteers after they were administered the bacteria, and it was not detectable in feces two weeks following the final dose, suggesting the bacteria only remained alive and active for a short period of time after being administered.
Being a Phase 1 trial, the primary goal is to test for safety. As the subjects in the trial were healthy, there is no data on how effective the bacteria would be in treatment conditions, but nitrates were found in all the subjects' urine, suggesting ammonia was being successfully mopped up at higher levels than normal.
Paul Miller, chief scientific officer from Synlogic, the company developing the novel engineered bacteria, says the data from this early human trial is promising and supports further development into these new kinds of living medicines. Miller notes that later this year more data should be published from further human trials into the efficacy of SYNB1020.
"The compelling data in this publication encouraged us to advance SYNB1020 into additional clinical studies and we look forward to presenting data from our trial, designed to evaluate the potential of SYNB1020 to lower ammonia in patients with cirrhosis, in mid-2019," says Miller.
This isn't the only research looking into genetically modifying common gut bacteria for positive clinical uses. Last year a team of researchers from Singapore revealed E. coli nissle could also be engineered heighten the production of a molecule called sulphoraphane, a known cancer-killing compound. Another study from last year suggested a different bacteria could be engineered to produce a chemical that helps relieve constipation. Both of those studies have yet to publish results in human subjects, so Synlogic's work is undoubtedly at the forefront of this new wave in genetically engineered probiotics.
The new study was published in the journal Science Translational Medicine.