Infection with the bacterium C. difficile is the most common and increasingly prevalent cause of diarrhea. Inthe United States, cases of C. difficile infection (CDI) are estimated to number 500,000 annually and to result inan estimated 15,000 to 30,000 deaths. The cost of these cases is thought to exceed $4.8 billion annually.CDI continues to cause discomfort, serious illness and sometimes death despite several available lines oftreatment. Current treatments include antibiotics, fecal transplant, and an antibody. The antibody representsa new approach to treating CDI by neutralizing toxins secreted by C. difficile rather than killing the bacteria orstopping their growth. One limitation of the antibody is that it needs to be delivered via an injection instead oftaken by mouth.The long-term objective of the proposed research is to develop a new treatment that binds to and neutralizethe toxins made by C. difficile and that may be taken by mouth. The treatment is based on a novel nanoCLAMPprotein similar to antibodies in its structure and potential to neutralize C. difficile toxin. However, comparedwith antibodies, nanoCLAMPs are much more resistant to the destructive effect of digestive enzymes.Resistance to digestive enzymes may enable patients to take this medicine orally and avoid a painful injection.The objectives of the current proposal are to1. Select lead anti-TcdB nanoCLAMPs with TcdB-neutralizing activity and developable biophysicalproperties.2. Assess dose-exposure relationship for anti-TcdB nanoCLAMPs in enteric capsules.3. Evaluate efficacy in acute and recurrence mouse models of C. difficile infection.
Public Health Relevance Statement: Infection with the bacterium C. difficile causes 500,000 case of diarrhea in the U.S. and over 15,000 deaths per
year. The long-term goal of the proposed work is to develop a new treatment that works in the gut to
neutralize toxins produced by C. difficile.
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