Using genetically modified microbes to deliver medicine in the microbiome. Day Two of CRL’s World Congress meeting.
Many of the medicines on the market are synthetic small molecule drugs, but one presenter at CRL’s World Congress meeting delivered a convincing argument in favor of using bacteria to cure rare diseases.
“We rely heavily on traditional animal models, like mouse models of disease and [large animal models],” said Kip West, Director of Pharmacology at Synlogic. “However our drug development [team] has been working on very nontraditional treatments – developing a novel class of synthetic biotic medicine by the marriage of synthetic biology and probiotic bacteria.”
West focused his talk mainly on the use of genetically modified E. coli to treat phenylketonuria (PKU) and maple syrup urine disease (MSUD); two rare inborn errors of metabolism that both result in toxic buildup of certain amino acids in the body. West described the process of developing E. coli strains that can theoretically be introduced to the patient’s microbiome to help break down these amino acids.
While the science behind these synthetic biotic medicines is complex, the concept is straightforward. The microbes themselves, in West’s examples, can be used to take the place of the missing parts of a patient’s metabolism that prevent them from breaking down certain chemicals. They are like the missing cog in a patient’s otherwise perfect digestive machine.
West described the tests that have been performed already on mice and larger animal models, and the results have been encouraging. The treated animals showed lower levels of toxic buildup of whichever amino acid was the target of the drugs, even in cases where the animals had been given high protein food. Traditionally, people with these diseases can only be treated by a restricted diet of little to no protein, which itself can cause issues. He said Synlogic has a projected schedule of human clinical trials that will take place this year and next.
At the end of the talk West was asked about any observed side effects in animal testing. He reiterated that not only were there no observed negative side effects, but that there was also no trace of the introduced E. coli found outside the gastrointestinal tract, and none in the excrement a week after treatment.
“One thing I didn’t say about this E. coli chassis is that it is non-pathogenic and non-colonizing,” he said. “So we envision it being a daily or a twice daily dose in these patient populations.”
West concluded by touching on possible future uses of the bug-as-drug model, such a targeted drug delivery for cancer patients.
“What we believe is that this class of living medicines may help to revolutionize how we think about the treatment of different diseases,” he said.