West Coast Editor
Hardly anyone who saw the U.S. Department of Health and Human Services' Pandemic Influenza Response and Preparedness Plan, released late last month, was surprised by the troubling language about avian flu strains, which "are becoming more capable of causing severe disease in humans" and have become endemic in some wild birds.
Just as concern over the West Nile virus - at least for this season - is subsiding, bird flu comes to the fore. St. Louis-based GenoMed Inc. has been working on both for a while, using angiotensin receptor blockers (ARBs).
"Angiotensin II is doing most of the damage," said David Moskowitz, chairman and CEO of GenoMed. "Even peanut doses of ARBs seem to have a very nice effect at suppressing over-exuberant immune systems."
The body's hyper-attack on foreign invaders apparently leads to self-destruction, a finding Moskowitz, a nephrologist, made by accident.
"I'm a kidney guy, and the last thing I ever thought I would work on is infectious diseases, and viruses in particular," he said. The discovery came as he was administering high-dose angiotensin I-converting enzyme (ACE) inhibitors to a patient with diabetes.
"The guy said his psoriasis was getting better," Moskowitz recalled, noting that ACE activity generates angiotensin II. "So I decided to start looking at more autoimmune diseases. I got a patient with alopecia, also a T-cell mediated disorder. There's no real treatment except getting steroid injections in your scalp. Very painful."
He put the teenage girl with alopecia on ARBs and, within 36 hours, her hair loss stopped. Moskowitz immediately began seeking more autoimmune subjects on whom to try the approach. "I got a whole bunch of chronic fatigue syndrome patients, about half of whom seem to do better," he said.
SARS reared its head in April 2003.
"They had been doing autopsies on people and found there were tons of white cells in the lungs [of SARS casualties], but hardly any virus," he said. "It looked like what was killing people was that they were overdoing their immune response. We tried to get some SARS patients but they were halfway around the world."
A better chance arrived with the advent of West Nile virus.
"It looked like the same pathology," Moskowitz told BioWorld Today, noting that the virus damages blood vessels in the brain "but it's the same picture - tons of white cells and hardly any virus. We had our own, homegrown viral epidemic' to test it in. We've got some nice data with humans for West Nile and we're hoping it's going to be applicable to most viruses," including avian flu.
"We don't have any people [who have contracted the avian strain] yet, but we're trying it in birds," he said. "It looks like birds get sick the way people do, though they get really sick, really fast. The dose may have to be higher in birds than in humans."
GenoMed has a multiyear collaboration with Italy's National Institutes of Health to test its patent-pending use of ACE inhibitors to treat avian influenza in poultry, but that deal is "specifically to address the havoc bird flu already causes in chickens," Moskowitz said. "They just did their first set of experiments. And now South Africa had an ostrich outbreak. They're apparently very susceptible birds, too. The idea is that all vertebrates overreact to this virus."
He visited the White House in July and homeland security officials in August.
"They've been looking for a universal virus antidote," Moskowitz said, and GenoMed might be onto just that. "So if a virus got released in the ventilation system of a building, you'd wind up taking an ARB," he said.
So far, the company has no government contracts but "we're trying to get them," he said. "There will probably be a lot more trips to D.C."
Meanwhile, GenoMed's protocol uses blood-pressure drugs that are safe and familiar to most physicians and veterinarians, and already carried in every drug store, he pointed out, which should make the approach that much more acceptable to doctors.
ACE inhibitors' range is even broader, he said.
"We've published a way of preventing 90 percent of kidney failure in the U.S., involving [those drugs] at higher than conventional doses," Moskowitz said. The only side effect is elevated potassium, which can be controlled with other drugs, he added.
"It looks like ACE is a master disease gene," he said.