Barbara Osborne, veterinary and animal sciences, and a small team of her colleagues involved in the startup medical research firm HasenTech recently were awarded two grants to advance their investigation of an exopolysaccharide (EPS), a sugar found on the surface of the bacterium Bacillis subilis. It can suppress an immune response and if translatable to use in humans, it holds promise of offering a new treatment for such conditions as irritable bowel disease (IBD) and other autoimmune diseases.
Osborne and colleagues have a one-year, $290,000 Small Business Technology Transfer (STTR) from the National Institutes of Health plus $100,000 seed funding for up to 18 months from this year’s round of the Institute of Applied Life Sciences’ (IALS) Manning/IALS Innovation Awards. This also provides business training and mentorship from IALS, the College of Natural Sciences, the Berthiaume Center for Entrepreneurship and the Isenberg School of Management to advance UMass Amherst-based translational and applied research and development to real-world use.
Osborne says, “Both grants will allow us to address the same question from different angles.” As she explains, humans are hosts for B. subtilis; it and its associated EPS are a natural part of our gut microbiome. People in Japan eat a fermented version of EPS called natto, she adds, which they believe to be beneficial.
Osborne’s long-time collaborator and friend, microbiologist and immune system researcher Katherine Knight at Loyola University, Chicago, discovered several years ago that mice induced to develop IBD are protected from the disease when treated with purified EPS.
Osborne recalls, “Katherine purified EPS and approached me with her results and asked whether we would test EPS in our mouse model of multiple sclerosis, a disease that is characterized by inflammation in the central nervous system. The mouse model, called experimental autoimmune encephalomyelitis, or EAE, is a very good model used by most MS researchers. Our preliminary data showed that EPS will suppress an autoimmune response in these mice and it did indeed save them from paralysis.”
Knight went on to test, in mouse models, purified EPS’s immune suppression effect in other inflammatory conditions including asthma and graft versus host disease (GVHD), which can be lethal to stem cell transplant patients, for example.
She and Osborne then approached Burnley Jaklevic, interim director of UMass Amherst’s Technology Transfer Office, about patenting the intellectual property and developing it for eventual use against autoimmune and inflammatory disease. The patent was granted last year, Osborne recalls. “Now we have the patent and our promising findings, and we began to think that maybe we could do something with this,” she says.
The HasenTech partners at this point approached Osborne’s collegues in veterinary and animal sciences, molecular biologist Lisa Minter, who has mouse models for both GVHD and aplastic anemia. Together they applied to NIH for an STTR to examine EPS in a humanized mouse model of IBS.
In a humanized mouse model, Osborne explains, mice are irradiated to destroy their immune systems, then repopulated with human immune cells. Those mice are then treated with mismatched donor cells so they get a version of GVHD with a response that can be observed in the human immune cells. “We want to show that EPS not only protects mice, but the humanized mice,” Osborne says.
“If we’re successful with that, the preclinical data will allow us to move on to the next phase,” she notes. However, there is a delivery problem, she adds. “We’d like to be able to deliver the EPS orally, not by peritoneal injection or intravenous methods. But if you feed purified EPS to a mouse, the indication is that the digestive system destroys it.”
To address this, she and her research partners approached food scientists Guodong Zhang and Julian McClements, asking if it might be possible to protect the purified EPS by encapsulation or some other method so it will survive the stomach and be released into the intestine. Once McClements and Zhang design the appropriate oral delivery strategy, Zhang will test the orally delivered EPS in his mouse models of IBD. McClements has an in vitro model of the digestive tract that he uses in his nutraceutical research, Osborne notes, but “EPS is a big molecule, probably larger than any he has ever worked with before, so our path to success is not entirely straightforward.”
She adds, “But if the food science people can figure this out, it will add nicely to the patent portfolio and our future research partnership opportunities with biotech firms. We’re hoping that someday, this may all lead to a new treatment for some of these very difficult diseases.”