C. difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea. In the U.S. alone, there are over 500,000 cases of CDI annually, with a mortality rate of up to 2.5% and costs of up to $3.2 Billion.
Current anti-CDI treatments--such as use of vancomycin or metronidazole--treat the infection. But unfortunately treatment failure and relapses are common using this approach.
C. diff, the causative agent of CDI, is a spore-forming bacteria. In fact, the resistant spores act as a Trojan horse to start the infection process. However, spores are dormant, and thus cannot cause the infection until or unless they are germinated. It is only at this stage of the lifecycle that C. diff spores become the toxin producing bacteria that leads to CDI.
Since C. diff spores germinate in the gut prior to CDI onset, Able Therapeutics is pursuing an entirely new approach: to target C. diff spore germination as an early, necessary step in CDI onset. The objective is to inhibit spore germination and to enable the development of unique prophylactic therapies for human CDI. Towards this goal, our scientists have found that bile salt analogs inhibit C. diff spore germination. More importantly, our scientists have shown that bile salt-treated animals are protected from CDI without overt toxicity. These promising results provide a clear link between anti-germination activity and CDI prophylaxis.
Normally, gut microbes form a barrier against C. diff colonization, but this protective function can be weakened when undergoing antibiotic therapy. Under these favorable conditions, C. diff spores interact with small molecule germinants, triggering a series of events that commit spores to germinate into toxin-producing bacteria.
Able Therapeutics is partnering with Tufts University and Wayne State University to develop compounds for CDI prevention. Our current lead compound is undergoing pharmacological, toxicological and efficacy profiling as a key step toward bringing a lead compound to clinical trials.