Biotech firm tries a novel tactic in fighting bacteria

A small Bothell-based biotechnology company is working on the medical equivalent of fighting fire with fire. To combat infections caused by bacteria, it is using a class of viruses that infect the bacteria themselves.

Phage Therapeutics Inc. hopes to use genetically engineered versions of these naturally occurring viruses, called bacteriophages, to treat diseases where antibiotic-resistant bacteria are becoming an increasing problem, such as staph infections and tuberculosis.

The company raised $5 million from a group of private investors in December to begin ramping up its research and development. Phage has so far received $3 million of that money and will receive the remaining $2 million before the end of 2001.

The first bacteria targeted by the company is the one that causes staph infections. The Centers for Disease Control has identified staph bacteria as the No. 1 cause of hospital infections. Between 60,000 and 80,000 patients die each year from various hospital infections.

Bacteriophages attach themselves to a host bacteria cell, such as staph, and inject the phage's DNA inside. The DNA then quickly reproduces hundreds of copies of the phage, often overwhelming and killing the bacteria in the process.

"For every bacterium there is a single phage that parasitizes it," or sets up a parasite/host relationship, said Richard Honour, the president and chief executive of Phage Therapeutics.

But sometimes phages do not reproduce quickly enough to kill the bacteria, and different strains of a particular bacteria may develop resistance to phages.

So, the company's challenge is to identify the right phages for a specific strain of bacteria, then genetically modify several phages into a single patented "superphage" that can attack several different strains of the bacteria at once.

"There are a ton of companies out there focusing on phage for different types of applications," said Robert Overell, a general partner at Seattle-based venture capital firm Frazier & Co.

Using phages to kill bacteria, though, "is a new approach in an area where new approaches are needed," he said. "There hasn't been a really new antibiotic invented in over 35 years. And some of these bacteria are becoming resistant to antibiotics, like vancomycin, which is usually the last line of treatment."

Antibiotics - such as penicillin, vancomycin and methicillin - are the most common treatment for staph bacteria. But of the 260,000 staph infections each year, about a third are resistant to one or more type of antibiotic, said Honour.

Phage Therapeutics has developed a phage - PX-10 - that kills the six most common strains of staph bacteria, including several that are resistant to antibiotics. PX-10 has been tested in preclinical trials with mice.

The company plans to continue animal studies this year and begin human clinical trials of PX-10 in the fall for the treatment of staph infections that cause corneal ulcers in the eye. Corneal ulcers can cause blindness in a matter of days if not treated, and antibiotics often take up to 10 days to be effective, said Honour.

In addition to staph bacteria, the company is also working on patented phages to treat tuberculosis and pseudomonas aeruginosa, a bacteria that often leads to the infection and eventual death of severe burn patients and children with cystic fibrosis.

Overell believes the company's strategy of starting with topical uses of phages outside the body and targeting staph, tuberculosis and pseudomonas "makes perfect sense." But he questions whether phage therapy will be effective in humans.

"Bacteriophage are not designed to live in people, so there will most likely be an immune response," against the phages, he said. "The question for me would be how long the phage has to stay in the body for the treatment to be effective."

The company has nine employees at its Bothell headquarters and employs 18 people at contract research organizations in the United States and Canada. It plans to hire three or four new employees in Bothell by the end of the year.

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