AmpliPhi BioSciences Corp. has presented data relating to the use of bacteriophages in the treatment of Pseudomonas aeruginosa (P. aeruginosa) at the 20th Biennial Evergreen International Phage Meeting held in Olympia, Washington, USA. P. aeruginosa is the major cause of lung infections in cystic fibrosis (CF) patients.
The presentation by Sandra Morales, Head of Research at AmpliPhi, entitled “Phage therapy for the treatment of P. aeruginosa lung infections in Cystic Fibrosis patients”, summarized data from three related studies demonstrating the potential for AmpliPhi’s proprietary bacteriophage mixes in the management of lung infection in CF patients.
“Taken together, these data present a compelling case for the potential of bacteriophages to treat P. aeruginosa infections in CF where the existence of biofilms and multi-drug resistant bacteria are a growing problem,” said Ms. Morales, who is based at AmpliPhi’s facility in Sydney, Australia.
“Biofilms are a major element in infection of the CF lung. Once a biofilm has formed, antibiotics are far less effective. Biofilms are a major line of defence for bacteria, contributing to antibiotic resistance. Bacteriophages are able to penetrate biofilms and replicate locally to high levels, to produce strong local therapeutic effects. Biofilm degradation by bacteriophages kills bacteria and could also potentially restore the efficacy of antibiotics” she added.
The first data set, based on results presented at the 2012 European Congress of Clinical Microbiology and Infectious Diseases conference, showed, in an in vitro model which resembled the environment in the CF lung, that bacteriophages can infect both mucoid and non-mucoid P. aeruginosa strains isolated from CF lungs, whether or not they were antibiotic resistant.
The second study, conducted in collaboration with the Pasteur Institute in Paris, examined a proprietary anti-Pseudomonas bacteriophage mix in the treatment of a murine model of acute lung infection.
The bacteriophage mix was shown to be as effective as a known high dose of antibiotic but also appeared to be more effective and faster at preventing the dissemination of the bacteria to lung and oropharynx. This data was presented initially at the 26th Annual North American Cystic Fibrosis Association Conference in 2012.
The third study presented research conducted in collaboration with the Brompton Hospital, London (see - Thorax 2012; 67: A50-A51 http://thorax.bmj.com/content/67/Suppl_2/A50.3) examining the effectiveness of a bacteriophage mix treatment in a murine model to both clear P. aeruginosa infection and limit inflammation.
The results demonstrated that the use of bacteriophage helps eliminate the infection earlier, which in consequence results in a lower inflammatory response.
“Our pre-clinical results to date are encouraging. There is a real need for novel therapies to treat bacterial lung infections. Phage mixes targeted at P. aeruginosa have the potential to be used as alternatives or adjuncts to conventional antibiotics. If the synergistic efficacy can be established, bacteriophage-based therapy will be of special importance to cystic fibrosis patients because P. aeruginosa is the most common bacteria that affects the lungs of a CF patient” said Philip J Young, CEO of AmpliPhi, who was also attending the conference.
“Examples of bacteriophage demonstrating clinical efficacy when used in regulated clinical trials are very limited. There is a real need to identify and test improved bacteriophages mixes in controlled clinical trials. We believe our preclinical data is supportive of this move as we plan to initiate clinical trials in 2014” he added.