BioWatch: Baltimore biotech turns to the past for cutting-edge treatment.

Intralytix wins Army contract to develop bacteriophages to fight diarrhea.

by Robert Rand Staff Writer

Alexander Sulakvelidze, chief scientist for privately held Baltimore biotech Intralytix, says the bacteriophage-based probiotic preparation shows promise for managing shigella infections, a "significant worldwide cause of diarrheal disease" " and apparently the U.S. Army agrees.

The company recently received a $100,000 phase 1 Small Business Technology Transfer grant from the Pentagon to develop the treatment, an alternative to antibiotics.

Shigella are "major gastrointestinal tract pathogens of particular concern" to the Army because U.S. troops are often stationed in countries where the disease is widespread, said Sulakvelidze, the company's principal investigator for the contract, in a statement.

There are about 164.7 million cases of shigellosis worldwide, almost entirely in developing nations, according to the World Health Organization. About half a million visitors from industrialized nations to developing nations contract the infection annually, and about 1.1 million people die from it each year, 61 percent of whom are children younger than 5.

There is no vaccine for shigellosis, and some strains of it have developed resistance to antibiotics, according to the federal Centers for Disease Control and Prevention.

Bacteriophages " highly specific viruses that infect bacteria " may be used to target "problem" bacterial species in the human gastrointestinal tract, according to Sulakvelidze.

"I'm so excited because these are brand-new, never-done-before" treatments, he said in an interview. "These viruses are the most abundant organisms on the planet. They're everywhere."

Because the bacteriophages kill specific bacteria, they were used "almost immediately in the early 20th century after their discovery," he said. Their specificity led to many successes, but also failures.

The discovery of antibiotics largely displaced bacteriophages as a treatment option for bacterial infections, but more in the U.S. and Western Europe than in the former Soviet Union and other Eastern European nations, Sulakvelidze said.

"I personally have taken them for therapeutic purposes, and never thought twice about them when I came to the U.S.," he said.

When a physician friend said he was having trouble treating a patient who had developed an antibiotic-resistant bacterial infection, "it dawned on me that they don't know about this alternative to antibiotics here," Sulakvelidze said.

Intralytix was the first company to receive approval from the Food and Drug Administration for food-safety applications for bacteriophages, he said. Now, the company is expanding into human therapeutics.

The oral treatment would be used preventively as a probiotic approach " somewhat akin to how active cultures in yogurt work in the intestinal tract to create beneficial flora " but specifically targeting potential shigella infections, he said.

"We started with shigella because of the mind-boggling mortality, 1 million a year," Sulakvelidze said. The impact of a successful treatment "could be staggering in the developing countries."

FDA approval is a long ways off. In fact, clinical trials likely won't start for at least three years, he said.

Still, Sulakvelidze is buoyed by the new Army contract, which he acknowledged is fairly small. It could lead to a phase 2 contract, which could be "significantly larger," he said. The company also has grant applications pending with the National Institutes of Health as it gets closer to conducting trials.