Thoughts on SGM – phage therapy

This week’s post is by Lauren Cowley, a PhD student in our lab studying the phage typing of E. coli O157. She was at SGM in Manchester last week and kindly agreed to write a blog post on one of the topics which made an impression on her; phage therapy…

 

Having just returned from SGM spring 2013 conference, I have been encouraged by the amount of chat about phage possibilities. There was an undercurrent of interest and research about phage peeping out from underneath the antibiotic tendencies that seemed to be presiding over the conference.

I respect the precedence of antibiotics due to the ever increasing need to address the issue of resistance and introduce new initiatives but was pleased to see a bit of a return to the biology of old and Delbrück’s wonderful world of phage biology.

A particularly interesting aspect of phage biology is the possible use of phages in therapy. As this tied into the wider SGM theme of novel antibiotics it was discussed at the live recording of TWiM (This Week in Microbiology). The main advocate of phage therapy was David Harper, a representative from AmpliPhi, a biopharmaceutical company that focuses on the development of a pipeline for bacteriophages for the treatment of bacterial infection.

Phages have long been used and were popular way back in 1919 for all kinds of diseases which are not bacterially related, David Harper showed a very amusing slide advertising phage therapy in the treatment of gall stones in 1919. However, now their real potential is better understood we can envisage their use in combating bacterial infections (including acne caused by P. acnes) once FDA approval is given.

Of course, just like any other potential drug, phages will need to gain regulatory approval. This is always a hurdle for novel therapies, never mind ones which are themselves ‘alive’. This struggle might be helped by other companies going through a similar process to gain approval for the use of viruses against cancer by e.g. Amgen/BioVex. In order to gain approval AmpliPhi will first have to isolate, characterise and purify their therapeutic phages and then put them through a series of clinical trials.

It may be that phages are just used to help existing antibiotics to work. Their potential to be aerosolised into the lungs of cystic fibrosis patients is exciting as the flora of these patient’s lungs is thought to be a major exacerbating factor in the disease and many other exciting projects are in the pipeline. However, there remain many unanswered questions; do you need to tailor a phage to a patient? Do you need to have a mix of phages for broader coverage in an active phage preparation? Will this approach enhance horizontal gene transfer?

A great advantage over current antibiotic therapy is that phages will undergo antagonistic co-evolution; a biological arms race with bacteria which we can harness for our benefit to counter resistance. To prevent horizontal gene transfer AmpliPhi only use obligately lytic, non-temperate phage so they cannot integrate into the host genome.

Two possible mechanisms for phage therapy are pre-defined phage mixtures that would be used for empiric therapy for specific bacterial infections or personalized medicine where an infected patient would be matched to a specific phage. A positive factor is that only a low dosage of phage is required in therapy as they will amplify once replicating at the target. Phages can also switch host-specificity and adapt to a range of bacteria that is present so this could be an opportunity as well as a problem when you want the paradoxical flexible specificity that is perfect in the antimicrobial world when an infection is growing and mutating in a background of commensal flora.

I personally think that phages hold a huge amount of potential in antimicrobial therapy and this field is definitely one to watch!

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