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New drug targets hamburger disease in children |
Dr. Glen Armstrong |
With outbreaks of E. coli reaching alarming levels throughout North America this summer, it's a relief to know a treatment for the nasty bacteria may be just around the corner.
The drug, called Synsorb Pk, is now in third-phase clinical trials at University Hospital and has so far shown promising results, says Dr. Glen Armstrong of the department of medical microbiology and immunology. Second-phase results, while inconclusive, demonstrated improvement in about 40 per cent of those treated, he says.
"Right now there's absolutely no treatment for this illness. Antibiotics are not recommended because, depending on who you believe, they have either no effect whatsoever, or may increase complications following infection." Without treatment, says Armstrong, about 10 per cent of infected children will develop severe problems such as renal failure or neurological dysfunction or kidney disease. Some cases can even be fatal.
Synsorb Pk is primarily targeted at young children, who are at greatest risk for contracting "hamburger disease" because of weaker immune systems and higher receptivity to the E. coli bacteria. The drug, essentially a combination of fine sand (silicon dioxide or powdered glass) and sugar, works by chemically binding to the toxin and flushing it out of the body.
"We attach the sugar molecules, which are the receptors for the toxin, to the surface of the particles. Any toxin that comes into contact with it will bind very tightly and be absorbed," he says. "It's kind of like a molecular lobster trap; the receptors are the bait-it gets in there but can't get back out again."
Because of its simplicity, Synsorb Pk is thought to be completely free of side effects, no matter how much is ingested. "The sugar is not toxic at all and neither is the sand, so we really didn't anticipate any safety issues or adverse reactions."
The drug's design is based on Dr. Ray Lemieux's pioneering research on synthetic sugars called oligosaccharides, which can be manipulated to bind to toxic proteins. For the E. coli study, Armstrong had a good deal of support from carbohydrate chemists Drs. Ole Hindsgaul, Monica Palcic, and Dave Bundle.
"In our lab we identify the receptors that toxins recognize on host tissues, and then we take that information to Ole, Dave and Monica," says Armstrong. "They come up with ways to synthesize these molecules in sufficient quantities to make Synsorb."
In the course of clinical trials, Armstrong and his colleagues have already been working on ways to make Synsorb Pk effective in more than 40 per cent of the infected population. "Our understanding of the way the organism causes infection is increasing as we're doing the study," says Armstrong. "Now we have some ideas as to how to improve the drug."
Clinical trials have so far been limited to Alberta, but since Synsorb Biotech Inc. (the company marketing the drug) has expanded into the U.S. and Argentina, Armstrong and his team will be able to conduct trials in those countries as well. If all goes as planned, Synsorb Pk should be on the market before the end of 1999.
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