Metabolic diseases may soon be treated by regular doses of synthetic biotics thanks to MIT spinout, Synlogic. The company’s goal is to reprogram bacteria located in the gut, turning them into what they call “living therapeutics.” These new medicines will help in the treatment of very serious diseases as well as rare genetic disorders affecting people across the globe.
Tim Lu and Jim Collins, co-founders of Synlogic, build synthetic biotics that not only track down, but also fix abnormalities at a metabolic level. These new biotics, when taken in either capsule or liquid form on a daily basis increase the amount of microbiota within the large intestines, reversing functionality loss within organs, such as the liver.
Lu states it has taken nearly two decades for this level of understanding about how microbes and the human body work together, which is expected to lead to big changes in the treatment of many worldwide diseases. It is finally understood that the bacteria that reside within the human gut have a very large influence on overall body health. In March 2016, Synlogic raised $40 million venture capital and was offered their first industry partnership with pharmaceutical company AbbVie. With the new partnership, the startup company is going to collaborate in the development of synthetic biotics in hopes of finding effective treatments for inflammatory bowel disease. The goal is to detect inflammation of the intestines sooner and create anti-inflammatory molecules or break down effectors that promote inflammatory.
As of April 2016, there are two drugs that are expected to begin clinical trials within the year: the first will treat urea cycle disorder (UCD) and the second will treat phenylketonuria (PKU). Synlogic’s drugs will flush toxic metabolites in both cases. UCD is caused by an enzyme deficiency which causes ammonia buildup in the blood. PKU is diagnosed when metabolic enzyme mutation leads to an excess amount of the amino acid phenylalanine. Collins says the drugs within the new clinical trials should be thought of as biological thermostats. These synthetic biotics will both detect and regulate the amount of a specific enzyme or metabolic byproduct. Collins is currently the Termeer Professor of Medical Engineering and Science in the Department of Biological Engineering and Institute for Medical Engineering and Science for MIT. He also is chair of the scientific advisory board within Synlogic.
Collins and Lu have been developing bacteria “genetic circuits” for over a decade at both Boston University and MIT. These studies have assisted in helping cause bacteria to use and save memories and perform logic. Because of this research, the team has been able to program bacteria to locate and cure certain infections. The Bill and Melinda Gates Foundation funded Collins back in 2011 to engineer bacteria that was able to both detect and treat cholera by creating antimicrobial peptides to target the health concern. In the past few years, Collins and Lu have worked together with venture capitalists in order to launch Synlogic. Their focus at start was merely to “commercialize a new class of therapeutics based on living cells.”
2014 was a big year for the low-profile company as they came forward and received their $30 million fund thanks to the support of the Gates Foundation and venture firms. Since that year, Synlogic has had their primary focus on programming E. Coli Nissle, which is a strain of bacteria widely used as a probiotic. Traditional methods have not been proven as safe or effective, so this was a great focal point for treatment research moving forward.
The main challenge within their research has proven to be tweaking dosages. Lu says, too little has just as much risk as too much. Too little can lead to no change, while too high of a dosage can lead to adverse side effects. With the right level of treatment, immune system function can be very positively impacted. Treating urea cycle disorder, for instance, is difficult and most often leads to a liver transplant in today’s world of medicine. Lu says Synlogic aims to find a way to treat UCD simply with a daily biotic that will decrease ammonia levels in the bloodstream, without the need to contact the blood directly. The biotic would convert intestinal ammonia into an amino acid, which would naturally excrete through the stool, minimizing both ammonia contact with the blood stream and ammonia levels within the blood stream.
Thanks to the deal with AbbVie, Collins says there are more possibilities for the treatment of many other conditions, including cardiovascular disease, and central nervous system disorders. There is still a bit of an uphill battle for Synlogic, as their research does not have a whole lot of clinical validation. The company plans to change that by creating precision-programmed synthetic biotics with higher potency. Synlogic treatments show high promise to reach what they call “clinical levels” of efficacy that is hard to find in the world of synthetic biology as of yet.