Related Experiment Video
Updated: Aug 3, 2026
Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
GT160-246, a toxin binding polymer for treatment of Clostridium difficile colitis
C B Kurtz1, E P Cannon, A Brezzani
1GelTex Pharmaceuticals, Inc., Waltham, Massachusetts 02451, USA. ckurtz@geltex.com
Abstract:
GT160-246, a high-molecular-weight soluble anionic polymer, was tested in vitro and in vivo for neutralization of Clostridium difficile toxin A and B activities. Five milligrams of GT160-246 per ml neutralized toxin-mediated inhibition of protein synthesis in Vero cells induced by 5 ng of toxin A per ml or 1.25 ng of toxin B per ml. In ligated rat ileal loops, 1 mg of GT160-246 neutralized fluid accumulation caused by 5 microg of toxin A. At doses as high as 80 mg/loop, cholestyramine provided incomplete neutralization of fluid accumulation caused by 5 microg of toxin A. GT160-246 protected 80% of the hamsters from mortality caused by infection with C. difficile, whereas cholestyramine protected only 10% of animals. Treatment of C. difficile-infected hamsters with metronidazole initially protected 100% of the hamsters from mortality, but upon removal of treatment, 80% of the hamsters had relapses and died. In contrast, removal of GT160-246 treatment did not result in disease relapse in the hamsters. GT160-246 showed no antimicrobial activity in tests with a panel of 16 aerobic bacteria and yeast and 22 anaerobic bacteria and did not interfere with the in vitro activities of most antibiotics. GT160-246 offers a novel, nonantimicrobial treatment of C. difficile disease in humans.
Insights
GT160-246 effectively neutralizes Clostridium difficile toxins A and B, preventing disease and relapse in animal models. This non-antimicrobial polymer offers a promising new treatment for C. difficile infections.
Area of Science:
- Microbiology
- Toxicology
- Pharmacology
Background:
- Clostridium difficile infection (CDI) poses a significant health challenge, often necessitating effective therapeutic interventions.
- Current treatments may have limitations, including relapse rates and the development of antimicrobial resistance.
Purpose of the Study:
- To evaluate the efficacy of GT160-246, a novel polymer, in neutralizing Clostridium difficile toxins A and B.
- To assess the in vivo therapeutic potential of GT160-246 against C. difficile infection and compare it with existing treatments.
Main Methods:
- In vitro assays using Vero cells to measure neutralization of toxin-mediated protein synthesis inhibition.
- In vivo studies using ligated rat ileal loops to assess neutralization of toxin A-induced fluid accumulation.
- Animal models (hamsters) to evaluate protection against C. difficile infection-induced mortality and disease relapse.
Main Results:
- GT160-246 neutralized C. difficile toxins A and B in vitro, inhibiting toxin-mediated effects on protein synthesis.
- GT160-246 significantly reduced fluid accumulation in rat ileal loops compared to cholestyramine.
- GT160-246 protected 80% of hamsters from mortality, prevented disease relapse, and demonstrated no antimicrobial activity.
Conclusions:
- GT160-246 is a potent neutralizer of Clostridium difficile toxins A and B.
- GT160-246 demonstrates significant therapeutic efficacy in vivo, outperforming cholestyramine and offering an advantage over metronidazole regarding relapse.
- GT160-246 represents a novel, non-antimicrobial therapeutic strategy for managing C. difficile disease.
