Using Flagellin to Prevent and to Treat Inflammation Associated Gram Negative Bacterial Infection

Case ID:
06-783

This technology provides a new method for treating inflammatory diseases by using a Gram negative bacterial component that results in increased tolerance and immunity.

 

Background & Unmet Need:

Despite advances of modern medicine, bacterial sepsis remains one of the major threats to human health worldwide.  In the US alone, it affects approximately 750,000 Americans per year, with an associated mortality rate of >28%.  Mortality is the result of excessive inflammation and reducing the inflammation by flagellin exposure, in combination with antibiotic treatment, may reduce septic shock and accelerate recovery after sepsis.  Research over the past several years has shown that the epithelial lining plays a key role in innate defense including recognition and response to bacterial infection.  However, the epithelia initiate an inflammatory response that, while necessary for clearance of bacterial infection, may cause tissue destruction such as that observed in septic shock, airway inflammation, ocular keratitis and inflammation bowel diseases.

 

Technology Description:

Our researchers have found that pre-exposure of epithelial cells to low concentration of bacterial flagellin induces “tolerance” as manifested by decreased proinflammatory cytokine production and reduced responsiveness to bacterial infection.  Instead of treating inflammation, this invention uses a Gram negative bacterial component to stimulate epithelial cells to a level that will not cause inflammation, but lead to tolerance alters the state of immunity in the body and blunt inflammation caused by Gram negative bacterial infection.  This approach will induce adaptations after initial inflammatory responses and may blunt inflammation in vivo without rendering the host susceptible to tissue destruction or systemic dissemination of infection and/or inflammation

 

Commercial Applications:

  • Therapeutic tool for the treatment of asthma
  • Anti‑inflammatory therapy for treating sepsis, pulmonary disease, Crohn’s disease, and inflammatory bowel disease

 

Stage of Development:

Preclinical; cellular studies performed

 

Competitive Advantages:

  • Use of Gram negative bacterial component does not cause inflammation
  • Use of Gram negative bacterial component leads to tolerance that decreases inflammation without increasing susceptibility to tissue destruction or systemic infection

 

Intellectual Property Status:

Patent application published

 

Related Publications or Citations of Work:

Kumar A, Hazlett LD, Yu FS. (2008) Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis. Infect Immun. 76(1):89-96.

 

Patent Information:
For Information, Contact:
Joan Dunbar
Associate Vice President for Technology Commercialization
Wayne State University
(313) 577-5542
jcdunbar@med.wayne.edu
Inventors:
Fu-Shin Yu
Ashok Kumar
Jing Zhang
Linda Hazlett
Keywords:
Anti-microbial
Asthma