Bacteriophages lack the ability to replicate on their own, so they've evolved to exploit host bacteria to stimulate the creation of progeny phages that ultimately destroy the host.
Each type of phage generally exploits only its particular bacterial host, so therapeutic phages also hold the promise of delivering specific elimination of disease-causing bacteria while sparing non-targeted bacteria, such as those found in the beneficial microbiota.
Our approach has several potential advantages compared to traditional antibiotic therapy: including:
All antibiotics have side effects, and some of these, such as allergic reactions, are common and manageable. Other side effects are more debilitating, including antibiotic-associated diarrhea caused by infection with Clostridium difficile bacteria.
Phage therapies have been administered to humans for nearly a century in Eastern Europe and the former Soviet Union with few reports of serious side effects.
Phage therapies are highly specific to their target bacterial species. They cannot kill mammalian cells and have minimal impact on beneficial bacteria.
Phages attack bacteria through a unique mechanism, therefore, they are likely to bypass the bacterial defense processes aimed towards antibiotics, thereby providing an alternative therapeutic option for difficult-to-treat, multi-drug resistant infections.
While resistance to phage infection can occur, phages and bacteria have been co-evolving for millions of years, meaning that phages have evolved to develop countermeasures. As in other predator/prey relationships, predators must develop new techniques to overcome the prey’s defense mechanisms.
Biofilms are almost impenetrable layers filled with aggregated bacteria and other extracellular components, which shield the bacteria. These complex communities of bacteria, present in the majority of infections, can render conventional antibiotics almost completely ineffective. By contrast, some bacteriophages are able to penetrate biofilms and replicate locally to high levels, producing a strong therapeutic effect.
Bacterial biofilms have been cited as a major line of defense for bacteria, contributing to their ability to persist in the presence of antibiotics. However, by targeting and destroying bacteria within biofilms using phages, this defensive shield is breached, leaving the remaining bacteria exposed and vulnerable to both the patient’s natural immune system and any available antibiotics.
AmpliPhi’s bacteriophage-based therapeutic approach selects and optimizes bacteriophage to target and kill the most clinically-relevant bacterial strains. Due to the self-replicating nature of bacteriophages, they can rapidly increase in numbers, allowing for a relatively small input dose to generate an effective therapeutic outcome.
Once AmpliPhi’s bacteriophage mix has infected the host bacteria cell, the resulting infection reprograms the bacteria to replicate itself, producing dozens or hundreds of new bacteriophages, which causes the bacterium to burst, thereby releasing the remaining phages to similarly infect neighboring bacteria. A typical bacteriophage infection cycle takes only a few minutes or hours, and only stops when the bacteriophages run out of target bacteria.
Once the bacteria has been eliminated, there is nothing left for the phage to infect, and it is removed from the body through normal clearance processes.
Currently, AmpliPhi is developing a pipeline of novel bacteriophage antibacterial therapeutics designed to be effective against antibiotic-resistant bacteria which can be delivered through multiple mechanisms for targeted therapy, including intra-nasal, topical and inhaled.