Protein Nanoparticle for IBD
Therapeutic Protein Nanoparticles for the Treatment of Inflammatory Bowel Diseases
Inflammatory bowel diseases (IBD) affect as many as 1.4 million Americans. IBD refers to chronic disorders of the intestinal tract, such as ulcerative colitis and Crohn’s disease, that produce symptoms such as abdominal pain and bloody diarrhea. In people with IBD, the body’s immune system mistakes food, bacteria and other materials in the intestine for foreign substances. In turn, the immune system attacks the cells of the intestines, by sending white blood cells into the lining of the intestines, producing chronic inflammation.
Existing treatments for IBD come with serious side effects — Emory's Andrew Neish, MD, however, has a solution. Along with his team, Neish, a pathologist at Emory Healthcare, has discovered that a protein called AvrA, derived from the bacterial pathogen Salmonella, is capable of suppressing inflammation in the intestinal tract. Neish and Julie Champion, PhD, a chemical engineer from the Georgia Institute of Technology ,aim to use synthetic AvrA proteins as new therapeutics for IBD by packaging them into very small particles designed to be absorbed into intestinal cells to stop inflammation.
"We're trying to isolate and refine the weapons that a pathogen uses to suppress the host immune responses and just leave the activities that can have a potential beneficial effect on other forms of inflammation," Neish says.
Over the years, Neish's research has included characterizing the immune signaling pathways that are involved during inflammation and bacterial infection. He says suppressing inflammation, which is a natural reaction of the body to injury, has always proved challenging. All the drugs currently on the market for IBD have severe side effects, largely because of the indiscriminate mode of action in blocking inflammation.
Most current therapeutics for IBD were generally developed by randomly screening chemical compounds or globally targeting general inflammatory regulators. They are then tested to see whether they have suppressive effects, and then evaluated for their toxicity and side effects.
AvrA, however, approaches the problem from a biological angle, rather than a chemical one. In using AvrA, Neish is exploiting a class of proteins that has evolved from certain intestinal bacterial pathogens. AvrA suppresses pathways without damaging the cell. Because AvrA proteins have evolved from pathogens that live inside intestinal cells as parasites, Neish explains that they aren't inclined to damage the intestinal cells.
"Essentially we're letting evolution do the work of drug discovery for us," says Neish. "We're trying to exploit the host-pathogen relationship that allowed bacteria to suppress inflammation as part of their lifecycles and develop therapeutics based on that." Cale Lennon, case manager in Emory's Office of Technology Transfer remarks that "This is truly an elegant and innovative approach for providing effective, localized treatment for intestinal inflammatory diseases.”
Neish draws a biological analogy with antibiotics, which are small molecules that have evolved in the interaction between fungi and bacteria. Similar to how antibiotics are produced from fungi to suppress competing bacteria in its environment, AvrA and related proteins evolved from pathogens to suppress inflammation in the intestines which is the pathogens environment.
"It's like an intracellular antibiotic," says Neish.
This research has extensive pharmaceutical applications, as inflammation occurs in a large a number of diseases including arthritis and psoriasis.
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