Bacteriophage cocktail shows significant promise for Clostridium difficile infections

Posted by ap507 at Jun 01, 2016 10:26 AM |
University of Leicester study uses phage-based therapy to address growing challenge of CDI

Issued by University of Leicester Press Office on 1 June 2016

  • Clostridium difficile infections (CDI) are responsible for approximately 39% of antibiotic-associated diarrhoea in the Western world causing 10% of deaths
  • Specific phage combinations caused complete destruction of C. difficile cells while in animal model dramatically reduced spread
  • Phage therapy prevents microbiome imbalance caused by traditional antibiotic treatment

Photographs of Professor Martha Clokie (credit to ‘University of Leicester’) available to download at: https://www.dropbox.com/sh/ol7w5p8cqzeng3j/AAB1izgmmAB0pZ78_oZuzx3Ja?dl=0

Watch a video of Professor Clokie explaining her research into bacteriophages: https://www.youtube.com/watch?v=wP1c7HJpeSU

A new University of Leicester study has confirmed the therapeutic potential of bacteriophage combinations to treat highly infectious bacteria C. difficile infections (CDI) while retaining a healthy gut.

A team led by Martha Clokie, Professor of Microbiology at the University of Leicester’s Department of Infection, Immunity and Inflammation, demonstrated that bacteriophage combinations significantly reduce growth of C. difficile cells and proliferation in complex models, whilst retaining healthy gut by preventing destruction of beneficial bacteria caused by traditional antibiotic treatment.

The study, which was funded by AmpliPhi Biosciences, is published in the peer-reviewed publication Antimicrobial Agents and Chemotherapy.

CDI is responsible for approximately 39% of the cases of antibiotic-associated diarrhoea in the Western world. Ten percent of CDI patients die due to lack of effective therapies. The main obstacles to preventing CDI are the existence of diverse C. difficile strains that vary in their response to antibiotics and the impervious nature of the C. difficile spores. 

Results from studies carried out by Dr Janet Nale in Professor Clokie’s laboratory demonstrated that specific phage combinations caused the complete destruction of C. difficile and prevented the appearance of resistant bacteria, while results of the complex models work showed that oral delivery of optimised phage combinations resulted in reduced C. difficile spread at 36 hours post-infection.

Additionally, the phage combination was able to kill 12 of the 13 C. difficile variants that are most prevalent in the UK, and were effective against the emerging variants that are increasingly causing concern in the UK, the US and more widely. The phage combination also reduced or completely prevented regrowth of C. difficile when compared to treatment with individual phages.

“Our data supports the therapeutic potential of phage combinations to treat C. difficile infections,” said Professor Clokie. “In particular, combinations of phages optimised in the laboratory setting were shown to be effective in the treatment of C. difficile in animals. Further refinements to our bacteriophage cocktails can be explored to maximise phage efficacy and to target the most dominant C. difficile variants.”

“Lab experiments, like this, allow us to see what effect specific phage combinations have on C. difficile in complex models. To see the effect of specific phage combinations in humans we would run an experimental trial with people.”

M. Scott Salka, CEO of AmpliPhi Biosciences, added: “The prevalence of C. difficile, the high costs of infection control and the challenge of finding alternative treatments, all contribute to the significant clinical and financial burden that CDI imposes on healthcare systems. The positive outcomes of these studies validate phage-based therapy as a promising approach that has the potential to address the growing challenge of CDI. We look forward to our continued collaboration with Professor Clokie to develop tailored and customised phage therapies for future clinical trials in humans.”

AmpliPhi Biosciences entered into its ongoing Collaboration and License Agreement with UK-based University of Leicester to develop a novel bacteriophage therapy targeting C. difficile in 2013.

  • ‘Bacteriophage Combinations Significantly Reduce Clostridium difficile Growth In Vitro and Proliferation In Vivo’ is published in Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01774-15

Ends

Notes to editors:

For more information contact Professor Martha Clokie at: mrjc1@leicester.ac.uk

About AmpliPhi Biosciences

AmpliPhi Biosciences Corporation (NYSEMKT: APHB) is a biotechnology company focused on the development and commercialization of novel bacteriophage-based antibacterial therapeutics. The Company's product development programs target infections that are often resistant to existing antibiotic treatments. AmpliPhi is collaborating with a number of leading organizations, including Intrexon Corporation (NYSE: XON), the U.S. Army, The Royal Brompton Clinic in London, UK and UK-based University of Leicester, to rapidly advance bacteriophage-based therapies. For more information, visit www.ampliphibio.com.

About Bacteriophage

Bacteriophage are naturally occurring viruses that are highly specific for the bacterial hosts they infect. They can rapidly kill their host, amplifying themselves in the process. Bacteriophage are unaffected by antibiotic resistance and are able to disrupt bacterial biofilms. Such biofilms are a major line of defense for bacteria, contributing to antibiotic resistance. Bacteriophage are able to penetrate biofilms and replicate locally to high levels, to produce strong local therapeutic effects.

Forward Looking Statements

Statements in this press release about the potential use of bacteriophages to treat bacterial infections, and the development of bacteriophage-based therapies are forward looking statements subject to risks and uncertainties, including without limitation the risk that the Company will not be able to successfully manufacture sufficient quantities of products to conduct clinical trials or commercialize products in a timely manner or at all, that AmpliPhi may not commence clinical trials or complete IND-enabling studies as expected, that the clinical trials will not be successful, that further development of the Company's products will require extensive and expensive nonclinical and clinical testing, may not be safe or efficacious, and may not be approved for marketing by the United States Food and Drug Administration or any foreign regulatory agency. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to AmpliPhi's business in general, see AmpliPhi's Annual Report on Form 10-K for the fiscal year ended December 31, 2014, as amended, filed with the Securities and Exchange Commission (SEC) on April 15, 2015.

Share this page: