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EXTON, Pa. -- ViroPharma Incorporated today announced the presentation of new data from preclinical studies of non-toxigenic Clostridium difficile at the fifth international meeting on the Molecular Biology and Pathogenesis of Clostridia (ClostPath), held June 21-25, 2006 in Nottingham, UK. These data showed NTCD to be protective against the currently circulating hypervirulent "BI" strain of C. difficile in a hamster model. Additional data presented during the meeting support the protection data by demonstrating that NTCD displays higher adherence to human mucosal cells compared to the BI strain and to traditional strains of C. difficile.
"These data are important, as they demonstrate that non-toxigenic C. difficile protects in an animal model against the dangerous hypervirulent strain of C. difficile that appears to be responsible for an epidemic of C. difficile-associated disease (CDAD) that is spreading throughout the U.S., Canada, and Europe," commented Colin Broom, MD, ViroPharma's chief scientific officer. "These data are not only significant, but essential as current and future therapies would need to consider effectiveness against this hypervirulent strain, which is associated with a substantial increase in the severity of CDAD in humans."
"These new adherence data are particularly important since intestinal mucosal cell adhesion is a potential virulence factor of the BI strain," added Dale Gerding, MD, associate chief of staff for research at the Hines VA Hospital. "The superior adherence of NTCD strain M3 compared to the hypervirulent BI strains also further corroborates the finding that it is highly protective in an animal model for CDAD against the BI strains. The high level of protection afforded by NTCD against this virulent epidemic strain in preclinical models of CDAD is encouraging for the development of this new therapeutic approach."
Protection data were described in an abstract titled, "Non-Toxigenic Clostridium Difficile (CD) Protects Hamsters against Historic and Epidemic Toxigenic 'BI' Strains," by K.J. Nagaro et al. In this study, the efficacy of NTCD in preventing disease in hamsters challenged with toxigenic BI strains was assessed. Animals were orally inoculated with one of two strains of NTCD (REA types M3 and T7) and then challenged with either a historic BI strain (BI1) or the BI strain causing the current epidemic (BI6), both of which have been previously shown to be 100 percent fatal in this model. Inoculation with M3 prevented fatal CDAD in nine out of 10 hamsters challenged with BI6 (p<0.0003) and 10 of 10 challenged with BI1 (p<0.00005). Inoculation with T7 prevented fatal disease in five of 10 hamsters challenged with BI6 (p<0.02), and 10 of 10 challenged with BI1 (p<0.00005). The authors concluded that colonization with NTCD, particularly type M3, is highly effective in preventing CDAD in hamsters caused by REA group BI strains, and provides a novel approach with the potential to prevent CDAD caused by the new epidemic strains in humans.
The adherence data were described in an abstract titled, "Hypervirulent Epidemic Strains of Clostridium Difficile Have Altered Host Cell Adherence And Protein Expression," by G. Vedantam et al. This study tested the hypothesis that increased adherence of the epidemic BI strain to mucosal lining contributes to the enhanced virulence of this strain. The results showed that an NTCD strain, REA type M3, displayed the highest adherence to Caco-2 human intestinal epithelial cells, followed by BI strains including the circulating hypervirulent strains (BI6, BI8 and BI17). Toxigenic, non-epidemic strains showed the lowest adherence. Epidemic strains have enhanced adherence to human epithelial cells which is associated with an increased expression of surface layer proteins which may allow them to predominate in their environment and cause more severe disease outcomes that are not solely toxin-related. The high level of adherence demonstrated by the NTCD M3 strain corroborates the high levels of protection observed against BI strain challenge in the hamster model.
Source: ViroPharma Incorporated
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