Bangalore-based GangaGen is currently in the process of developing a bacteriophage-based antibiotic drug potent enough to destroy resitant strains of bacteria.
Named StaphTame, Gangagen’s P128 is a recombinant protein meant for the topical prevention and treatment of Staplylococcal infections, including infection with methicillin-resistant Staphylococcus aureus (MRSA).
MRSA is a bacteria resistant to multiple antibiotics. MRSAs, normally acquired from hospitals, often cause serious, and even fatal, infections.
MRSAs are getting increasingly resistant to more and more available antibiotics including to even vancomycin – the treatment of last resort.
Generally, MRSAs spread from infected patient’s nose and 30-50% of the population carries S. aureus in their nose.
As much as 125,000 total and 95,000 invasive methicillin-resistant S. aureus (MRSA) and 165,000 methicillin-sensitive (MSSA) infections and 19,000 deaths occur due to MRSA each year, in US alone. Most of these deaths are due to healthcare-acquired MRSA infections.
GangaGen is currently testing StaphTame in pre-clinical toxicology studies in the final stages. The P128 protein has been tested against over 200 strains of S. aureus, more than half of which are methicillin-resistant. The data showed that StaphTame and has proved capable of killing 56 Japanese isolates, 119 Indian isolates and 8 Canadian isolates.
StaphTame, which contains P128 protein was developed based on a key protein from bacteriophage. When phages first interact with a bacterial cell, they damage the cell wall in order to insert their genetic material.
GangaGen has identified the active portion of the phage molecule that causes this damage, and coupled it with another protein sequence that allows binding to the surface of Staphylococcus.
The hybrid molecule is capable of binding to, and damaging the surface of, all strains of S. aureus tested. This damage results in the death of the bacteria.
No dose-limiting toxicities have been seen in these studies. the company has already planned Phase 1/2 study that will include safety, dosing, and preliminary efficacy.
GangaGen has completed formulation with StaphTame for intranasal use and has scaled up manufacturing to support clinical studies.
The company also held a pre-IND meeting in March, 2010 with the US FDA exploring the possibility of filing the StaphTame as a new drug to treat resistant bacteria.
What is a bacteriophage antibiotic?
Bacteriophages are viruses that parasitize and kill bacteria. Bacteriophages are highly specific, naturally occurring agents that enter bacteria and destroy them.
Bacteriophages are used to cure diseases particularly where antibiotics have proven to be either ineffective or where the disease-causing bacteria have built resistance against the prescribed antibiotics.
A bacteriophage attaches itself, through specific receptors, to the surface of the host bacterial cell and injects its nucleic acid (DNA or RNA) into the bacterium. The bacteriophage DNA redirects the bacterial cell’s biosynthetic machinery to produce hundreds of new bacteriophages which, when released, destroy the bacterial cell.
The new bacteriophages invade other bacteria in the vicinity and the process is repeated about every thirty minutes until all of the bacteria are eliminated. At this time, the bacteriophages, being non-living entities, self-eliminate because the bacteria that they require as hosts no longer exist.
In addition to treating bacterial diseases, bacteriophage preparations can be used as prophylactics to control or prevent epidemics.
Bacteriophages have been found safe for treating a variety of infections. They are non-toxic and cannot act on anything except the bacteria to which they can attach and into which they can inject their nucleic acid.
Bacteriophages will specifically target the harmful bacterium, eliminate it, and leave the beneficial bacteria intact.
Bacteriophages are non-living entities. Bacteria can cause disease partly because they are living entities that feed on other living organisms e.g. humans, animals, plants, etc.. Bacteriophages cannot cause disease to humans, animals, or plants; they can only cause harm to bacteria.
Unlike antibiotics, bacteriophages evolve with bacteria to combat bacterial resistance. Resistance to bacteriophages appears to be limited so far.
Bacteriophages have a distinct advantage over antibiotics in overcoming resistance because bacteriophages evolve faster than bacteria and those that develop against resistant bacteria can be isolated in days or weeks.
GangaGen, Inc. is a biotechnology company focused on the development of proprietary products for the prevention and treatment of bacterial infections, particularly infections that are resistant to antibiotics. The Company’s technology has arisen from its studies of bacteriophage, nature’s antibiotics.