Friday, March 23, 2007

 

Bacteria-eating Virus--new antibiotic

Nature’s Medicine

Set to hit the market within a year, Bangalore-born Gangagen’s natural bacteria killer could spell the end for antibiotics
P. Hari

Few businessmen would spend a lot of time talking about a harmless virus. But this virus, called a phage, kills bacteria that are dangerous to human beings. You could use it as a drug, if we knew how to tame it and get it to the right place. Some institutions and a few companies have tried to do it for decades, but with limited success. But now, an Indian-founded company seems to have achieved just that. Within a year, it will launch the first, phage-based antibacterial drug in the world.

Born in Bangalore, registered in Delaware, US and with an office in the Silicon Valley, Gangagen is still an oddity among technology companies. Few companies would be brave enough to bet an entire business on phages. It was born when J.Ramachandran, after retiring from Bangalore-based AstraZeneca R&D, decided to take up a challenge that everybody had left unfinished: conquer the mighty bacteria. It was a brainwave while watching a programme on the BBC. He knew nothing about phages when he set up the company. He still got $2 million (Rs 8.8 crore) from Silicon Valley-based ICF Ventures.

Ramachandran got scientists excited about his venture. In Ottawa, Canada, where he set up a subsidiary, he got some very experienced hands. Michel Chretien, well-known physician and brother of former Canadian prime minister Jean, became the chairman. Rainer Engelhardt, scientist and entrepreneur, became the president of the Ottawa company. Kishore Murthy, biologist and experienced phage researcher, became the chief scientific officer. This team, along with a few more scientists in Bangalore, took Ramachandran’s initial ideas and developed them into veterinary applications. Its first drug, to treat Escherichia Coli in cattle, is in advanced clinical trials. Between them and few other friends and board members, they also managed to raise substantial funds.

After ICF Ventures, most venture capitalists did not share the excitement of their scientists. Gangagen also refused to do services till it finished developing its product. Yet, its team managed to raise money after the initial rounds: $1.9 million in 2003 from board members and other initial investors; $2.5 million (Rs 11 crore) in early 2006 from a few more investors; and $4.5 million (Rs 19.8 crore) in September 2006 from several other individuals. What puzzled VCs was that Gangagen had no drug in the conventional sense.

Old Science, New Techniques


The Russians, during the time of Stalin, were the first to use phages to treat infected wounds. Even now, former Soviet Union countries use phages for therapy. The Tbilisi Institute in Georgia is a specialist institution for researching phage therapy. But the method has not caught on worldwide because of several scientific and business reasons. There is no commercial phage product that can treat bacterial infections either in humans or animals. Gangagen’s would be the first. And it aims to treat the problem at the source.

The gut of a cow is a reservoir of E.Coli 0157:H7. The cattle do not fall ill, but the bacterium runs amok when it emerges from the animals. The dung of cattle is rich in E.Coli, which seeps into the ground water. It also contaminates vegetables when dung is used as manure. When the cattle are slaughtered, the bacteria contaminate the meat, which is a major source of infection in developed countries. If you could eliminate E.Coli from cattle, you could also reduce the chances of infection in humans. Gangagen had patented some ingenious methods of using phages to treat humans, but those will come later. Veterinary applications are easier from a regulatory point of view.

It is not as if other companies had not tried to treat cattle using phages. OmniLytics, a company based in Utah, has a formulation that is sprayed on the skin of the animal. This method does work to an extent, but cannot kill the bacteria inside the animal’s body. Gangagen has developed pellets mixed with the feed — using a patented method — that take the phages directly to the source. The pellets are stable inside the cow’s stomach, but release the phages when inside the intestine, where they wipe out the E.Coli. The phages are so selective that they kill only E.Coli 0157:H7, leaving other bacteria alone. Says Ramachandran: “The best thing about phage therapy is the specificity. Unlike antibiotics, phages do not kill useful bacteria.”

Gangagen has tried the method in about 80 animals. The pellets are given every day to the cattle one week before slaughter. Thus, their guts are cleaned of E.Coli by the time they are killed. By the end of the year, it would have conducted trials on 400 animals. It is also developing phage-based products to treat salmonella and campylobacter infections, both common in the dairy industry. The veterinary market for treating infections is large. In North America alone, the dairy industry loses over $3 billion a year due to infections. Around $5 billion is spent on treating antibiotic-resistant infections in domestic animals.

Gangagen has tied up with Elanco Animal Health, a division of Eli Lilly Canada, to market the veterinary product all over the world. Incidentally, Eli Lilly was the first company in the world — in the 1930s — to pursue phage therapy. It later gave up because the method was not scientifically and commercially viable at that time.

Gangagen, however, has solved these problems with some recent research and patents. The major scientific problem is that phages kill bacteria and then come out of them in amounts numbering in the hundreds of thousands, and scattering bacterial toxins in the process. The commercial problem was that phages were known long ago — one cannot get patents on old knowledge. Gangagen, however, found a new technique, which stops the phage from coming out of the bacterium after it kills it. It was then granted a few more patents, including one to use the phage as a vaccine. Gangagen had solved both the commercial and scientific problems in one stroke.

The End Of Antibiotics?


Sometime next year, Gangagen could start human trials on topical applications of phages. A specific target is the bacterium staphylococcus, an antibiotic-resistant bacteria that causes smoldering infections in wounds, particularly when acquired from hospitals. Staph, as this bacterium is usually called, lives in our nasal cavities and is a major cause of infection after surgery. Use of nasal sprays a few days before surgery could eliminate the problem. To keep the costs down, Gangagen had not used its patented genetically-engineered phages on the veterinary product. But human applications would necessitate the use of its genetically-engineered phages that kill the bacteria but not scatter the toxins.

Antibiotics were once considered magic bullets to cure any infection. However, it is now apparent that humans are losing the battle against bacteria. Phages are nature’s own cure, which is preferable even in animals. Says Tim Guichon, managing partner, Feedlot Health Management Services in Alberta, Canada: “There is a feeling among the public that large-scale use of antibiotics in animals increases the chances of resistance in human infections as well.” If phage therapy becomes widespread in a decade, Gangagen would almost certainly be the pioneer.



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