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Why C. difficile-defanging mouse cure may work in people, too

CdiffI wrote a news release last week about a study just published in Science Translational Medicine. The study, despite it having been conducted in mice, not humans, received a fair amount of coverage - by The Washington Post, Yahoo!, Fox News, NBC, CBS and Reuters, among other places - and deserved the attention it got. It demonstrated the efficacy of a small-molecule drug that can disable the nasty intestinal pathogen C. difficile without killing it - and, importantly, without decimating the "good" bacteria that populate our gut by the trillions.

That's a big deal. If you want to see a lot of ugly weeds pop up, there's no better way to go about it than letting your lawn go to hell.

C. difficile - responsible for more than 250,000 hospitalizations and 15,000 deaths per year in the United States and a $4 billion annual health-care tab in the U.S. alone - is typically treated by antibiotics, which have the unfortunate side effect of wiping out much of our intestinal microbe population. That loss of carpeting, ironically, lays the groundwork for a dangerous and all-too-common comeback of C. difficile infection.

A question worth asking about this study, conducted by what-makes-pathogens-tick expert Matt Bogyo, PhD, and a team of Stanford associates: Why should we think that what works in mice is going to work in people?

The only sure answer isn't a torrent of language but a clinical trial of the drug, ebselen, in real, live people with C. difficile infections or at risk for them. (Bogyo has already started accumulating funding to initiate a trial along those lines.)

But there's also reassurance to be drawn from the fact that ebselen isn't an entirely exotic newcomer to the world of medical research. As I noted in my release:

Bogyo and his associates focused on ... ebselen because, in addition to having a strong inhibitory effect, ebselen also has been tested in clinical trials for chemotherapy-related hearing loss and for stroke. Preclinical testing provided evidence that ebselen is safe and tolerable, and it has shown no significant adverse effects in ensuing clinical trials.

In addition, gut-microbe guru and auteur Justin Sonnenburg, PhD (a co-author on this study), told me when I interviewed him about the study:

This is one of those instances where there isn't a lot of esoteric mouse biology involved. The drug, for instance, doesn't even have to get into the blood stream, because the action is taking place inside the gut. And the mouse turns out to be a great model. It's remarkable how this little rodent recapitulates so many features of the human version of C. difficile infection.

Much has been said, in particular by Stanford immunologist Mark Davis, PhD, about the differences between mice and us. As Davis once told me in an interview for a Stanford Medicine article, "We’ve cured cancer and autoimmune disease in mice many times over ... [A] colleague ... often starts his talks with the salutation: 'For the mice in the audience, I have wonderful news!'

Maybe this time the wonderful news will apply to us, too.

Previously: Study means an early, accurate, life-saving sepsis diagnosis could be coming soon, Cat guts, car crashes and warp-speed Toxoplasma infections, Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?, Joyride: Brief post-antibiotic sugar spike gives pathogen a lift and Immunology escapes from the mouse trap
Photo by Kateryna Kon/Shutterstock

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