In this section
Mouse Models Reveal Drug that Safely Disarms C. Difficile
One of the biggest problems faced in dealing with the Clostridium difficile pathogen is that treatment kills healthy gut microbes alongside the dangerous bacteria. Using mouse models, a study led by Stanford University may have solved this problem by tackling toxins within the pathogen, instead of aiming to kill it with antibiotics.
Up to now, treatment for severe C. difficile has been either faecal transplants that return healthy bacteria to the patients’ gut, or antibiotics, which do not always work. This study used a small-molecule anti-virulence agent called ebselen; this has already been tested in clinical trials for its effectiveness in treating hearing loss and strokes in chemotherapy recipients. It works by inhibiting the activity of the two toxins produced by the pathogen (referred to in the study as Toxin A and Toxin B) that cause the symptoms of C. difficile.
The team of researchers behind the study, led by Dr Matthew Boygo, began screening small molecules that could arrest the protease activity of these toxins. If this activity could be stopped, the toxins could not activate the cells that cause inflammation and the destruction of good bacteria. After experimentation on 120,000 small molecules to see which drugs inhibited protease activity in Toxin B, Dr Boygo et al chose to investigate ebselen.
The team discovered that mice survived after being injected with Toxin B molecules that contained ebselen. Mice injected with ebselen-free Toxin B died within 48 hours. In a second round of tests, the team gave mice antibiotics, and then infected them with C. difficile bacteria before giving them ebselen orally. The researchers then observed what Science Daily describes as “a nearly complete block of inflammation and damage to colon tissue”. In short, the ebselen prevented the C. difficile pathogen from doing any damage, without killing healthy bacteria or damaging gut tissue.
The dangerous nature of C. difficile means that moving this drug onto clinical trials is urgent; the process will hopefully be sped up by the fact that ebselen has already performed well in clinical trials. This study reinforces the reality that mouse models need to be utilised in the most effective and data-rich way possible, to allow the swift progression of beneficial drugs through the drug discovery pipeline.
Our Actual HCA home cage analysis system offers drug discovery insights that are crucial in studies like this one. It provides 90% more data than standard methods using 50% fewer mice, offering high throughput and low waste. For information on ActualHCA, click here. To read the study in Science Translational Medicine, click here. Alternatively, click here to read the article in Science Daily. If you have any questions, get in touch today.