Fighting drug-resistant bacteria, and winning patent – GangaGen, Bangalore

GangaGen is a Bangalore-based biotechnology company focused on the development of proprietary products for the prevention and treatment of bacterial infections, particularly infections that are resistant to antibiotics, through the application of contemporary molecular and clinical sciences. GangaGen’s technology has arisen from its studies of bacteriophage, nature’s antibiotics.In an interaction with the founder J. Ramachandran, we relived the saying, ‘Passion lies at the heart of any venture.’ Ramachandran is very driven in his cause to make our world bacteria-free. Somewhere, I believe that in his cause rest our own cause and aspirations. Many of us have witnessed the debilitating effect of drug-resistant infections around us; it’s time to celebrate this silent champion of bacteriophage.

“During my work – as the Head of Astra Research Centre India (1986 - 1994), Astra Biochemicals (1995 -1998), and AstraZeneca India (1998 - 2000) – I realised that the overuse and misuse of antibiotics was largely responsible for the resistance to antibiotics, a major problem in the control of bacterial infection,” says Ramchandran. He also realised that new antibiotic is not the answer, because the resistant pathogens are capable of developing resistance to newer agents rapidly.

Ramchandran continues, “Additional motivation to look for novel strategies for battling antibiotic-resistant infection came from the demise of my mother, who was in very good health. At the age of 93, she had a fall and broke her thigh. She underwent successful surgery lasting 4½ hours, only to succumb to hospital-acquired pneumonia which did not respond to antibiotics.”

In looking for alternatives to antibiotics, Ramchandran came upon bacteriophages which had been used extensively in the former Soviet Union but not in the West. He also found out that the very first observation of the power of phages for killing bacteria had been made in India, in 1896, when a British scientist named Hanbury Hankin, working in the Government Laboratory in Agra showed that the waters of Ganga and Jamuna could eradicate Vibrio cholera cultures.

“So, I started GangaGen in late 2000, to develop bacteriophages and phage-based therapies for the control of infection. GangaGen’s first target is Staphylococcus aureus, the resistant form of the organism, namely, Methicillin Resistant Staph Aureus (MRSA), a dreaded superbug posing severe problems in hospitals. We started developing broad host range phages against Staph Aureus, but soon realised the limitations of DNA-containing entities for therapy, and focused on one key element that enables the phage to breach the bacterial cell wall and inject its DNA into the bacterium. We identified the gene coding for this putative enzyme, which we named, ‘Tail Associated Muralytic Enzyme,’ or StaphTAME.”

The gene was cloned, expressed and optimised to kill all clinical isolates of Staph Aureus including all MRSA, which is currently the most serious hospital-acquired infection. GangaGen’s first product, StaphTAME (also known as P128), for the control of Staph including MRSA is currently undergoing clinical trials which have already demonstrated safety in humans,” says Ramchandran. “All preclinical development of StaphTAME has been completed and a successful pre-IND meeting with the US FDA has been concluded. GangaGen is preparing to conduct clinical trials of StaphTAME later this year both in the US and in India. StaphTAME is a recombinant protein that kills MRSA and all Staph bacteria rapidly (in minutes) by a novel mechanism,” says Ramchandran.

On what more is happening at his firm, Ramachandran says, “Pseudomonas aeruginosa is the most antibiotic-resistant pathogen after MRSA and is the source of major infection in burns and wounds. GangaGen is developing a proprietary product for the control of Pseudomonas aeruginosa that is currently undergoing preclinical development. GangaGen hopes to advance this product into clinical trials next year. Also, GangaGen’s research team is also engaged in the discovery and development of phage-based products for the control of other pathogens, including Clostridium difficile, which often emerges as a secondary infection following antibiotic treatment and is rivalling MRSA as a hospital-acquired infection in the UK.”

Fact sheet

Two patents on the Lysis-deficient phages were issued to GangaGen by the US Patent Office in 2005.

GangaGen started in the year 2000 and is headquartered at Yashwantpur in Bangalore.

Inspiration

“…Mother, hast thou power to save

Only, nor dost thou grow old near Sagar, nor our vileness stains,

Ganges, thy celestial wave.” (To the Ganges, by Sri Aurobindo)