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The daily life of a cystic fibrosis patient is burdened by treatments to break up excess mucus in their lungs. But a new compound discovered in Florida red tides could make their treatments more convenient. This ScienCentral News video has more.
Red Tide Toxins
Every morning, Nicole Kelly starts her day twice, once at five and then again shortly after seven. Kelly is among 30,000 Americans with cystic fibrosis, a disease that makes it tough for her to breathe because excess mucus collects in her lungs. The mucus is a haven for bacteria that makes her particularly susceptible to infections and pneumonia. So, two times in the morning, and at least twice more during the day, she uses a nebulizer, a machine that pumps mists of antibiotics and mucus-clearing agents into her lungs.
"I'm up at five in the morning. I do my nebs, then I go to the gym," Kelly says. "Then I come back home by seven to get my daughter up for school and then I get her off and then I start my day again with another set of treatments."
The average life expectancy for people with cystic fibrosis is between 32 and 33 years. Those who live longer, like Kelly, 38, will tell you there is nothing convenient about her daily treatments or the fact that she lugs her nebulizer around like a second pocketbook. But unexpected findings by marine biologists studying Florida red tides—the algae known for poisoning fish—may provide a new and more effective class of drugs to treat cystic fibrosis. It's a discovery that could transform Kelly's bulky nebulizer into an inhaler that would fit in her pocket and free her to take a puff only when she needed it.
Daniel Baden, director of the University of North Carolina at Wilmington's Center for Marine Science, led a study funded by the National Institute of Environmental Health Sciences that assessed the effects of airborne red tide toxins on human health. He discovered that the same microscopic marine algae, Karenia brevis, which produces toxins that make beachgoers cough, sneeze and wipe tears from their eyes, also produces good chemicals called antitoxins. "This antitoxin can prevent the effects of the toxin, it can reverse the effects of the toxin, and it actually can be protective if it's provided before toxin exposure," says Baden.
The researchers noticed there were times when high concentrations of the red tide algae did not produce allergic reactions among coastal locals. They figured something must have been counteracting the effect of the toxins. Close examination led to the identification of the antitoxin, which was about half the size of the toxin.
Marine biologists discovered this microscopic algae, called Karina brevis, produces both toxins and antitoxins. image: Daniel Baden
The production of toxins and antitoxins depends on the lifecycle of the red tide algae. When the individual algae are becoming more concentrated and increasing their population count, they produce little of the toxin and more of the antitoxin. When they're just floating about, or in their "stationary phase," as Baden calls it, they produce more toxins. "The antitoxin inhibits the toxin much in the way that young children play musical chairs," says Baden. "The toxin sits in the chair, and increasing concentrations or increasing amounts of the antitoxin, act to sit in the chair and prevent the toxin from sitting down."
Both the toxins and the antitoxins bind to the same molecular site in our bodies. This molecular union occurs in the brain and in the nerves. As a result, if the antitoxin fills the binding site first, then the toxin cannot induce an allergic reaction. Though similar binding sites have not yet been identified in the lungs, Baden and his colleagues think they are there, helping to control bronchoconstriction, the opening and closing of tiny airways in the lungs.
In the January 1, 2005 issue of the American Journal of Respiratory and Critical Care Medicine, Baden and his colleagues reported that a natural and a synthetic version of the antitoxin prevented bronchoconstriction and the accumulation of mucus in lungs of sheep. When the researchers gave the sheep both the natural and the synthetic antitoxins, the effect was even better.
The antitoxins do two things to clear lung mucus: First, they thin the mucus by moving salts smoothly through tiny channels on the surface of the lungs. (Cystic fibrosis patients have a genetic mutation that blocks these salt channels, leading to mucus build-up and permanent lung tissue infection.) Second, the antitoxins make the tiny cilia which line the inner surfaces of the lungs beat faster. "Put those two together, and mucus clears more readily," says Baden.
"The fact that this affects salt channels is the serendipitous thing that is hopefully going to help us develop new drugs," says Robert Giusti, Nicole Kelly's physician and director of the Cystic Fibrosis Center at Long Island College Hospital in Brooklyn, New York. Giusti admits it's too early to tell how effective the antitoxins will be relative to other cystic fibrosis treatments, but he says the fact that a very small quantity of the antitoxin was needed to be effective, even deep inside the lungs, is promising in terms of side effects.
Baden says that it will take approximately ten years to determine if the antitoxin is safe and effective for cystic fibrosis patients and to develop it into a convenient inhaler. In the meantime, Giusti is telling Nicole Kelly and his other patients to keep themselves well nourished and to exercise so they have the stamina to fight off infections.
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