Drugs from bugs: NIH grant supports development of unique psoriasis treatment at Kansas State University
Thursday, Nov. 1, 2018
MANHATTAN — Philip Hardwidge, a microbiologist and biochemist at Kansas State University, has received a $218,593 grant from the National Institutes of Health for enhancing the development of drug treatments for psoriasis, a chronic inflammatory skin disease.
The study, "Using anti-inflammatory bacterial proteins to treat psoriasis," is in collaboration with Christian Rueter and Karin Loser, both with the University of Munster, Munster, Germany.
Hardwidge's research is focused on how bacterial virulence proteins can be developed into anti-inflammatory drugs. This work is derived from the "drugs from bugs" concept. This term refers to the concept that basic research focused on understanding how microbial pathogens have evolved to control and modulate the host immune system during infections can be exploited for novel immune-modulation strategies to treat inflammatory diseases that are unrelated to microbial infections.
"Overactive immune responses are often the causes of different autoimmune or chronic inflammatory diseases such as psoriasis," said Hardwidge, a professor of diagnostic medicine and pathobiology in the College of Veterinary Medicine. "Although certain immunosuppressive drugs and various biologics have been used successfully to treat these disorders, these drugs have notable limitations, including the need for many of them to be administered systemically. These existing drugs can have adverse side effects and high costs."
Through this grant, Hardwidge and his research team plan to make a more efficient, cost-effective drug by engineering Escherichia coli and Yersinia enterocolitica — the bugs — virulence proteins to function as cell-penetrating molecules that can enter eukaryotic cell membranes autonomously — the drugs.
Hardwidge said the proposed approach of utilizing these effectors as anti-inflammatory proteins can then be used to treat inflammatory skin diseases. He said one of the obstacles is how the body's immune system can develop antibodies that could counteract efforts to treat the condition.
"We are studying the effects of the direct application of the proteins on skin cells and whether that will suppress the development of psoriasis," Hardwidge said. "Our preliminary data are quite positive, and we'll be looking to see whether the treatment continues to be effective, even following long-term treatments. One advantage is that our products are administered topically, to the site of inflammation, potentially eliminating concerns about systemic immune suppression."
This project was initially conceived and developed after a serendipitous meeting between Hardwidge and Rueter at a Keystone Symposium in 2011, where each project partner realized that the other was studying complementary aspects of similar projects.
Hardwidge said Kansas State University is a strong supporter of international research collaborations.
"Scientific collaborations that ultimately lead to significant extramural financial support take significant time and institutional support to drive a project from the conceptual stages to a final product," he said.