Research with Red Tide Toxin Yields Potential Therapies for Cystic Fibrosis
Researchers working with Florida red tide discovered two new compounds
that may treat mucus build-up associated with cystic fibrosis and
similar lung diseases. Preliminary studies show these compounds
improve the flow of mucus through the respiratory tract, allowing
airways to clear more quickly and efficiently.
"These compounds are excellent candidates for the development
of an entirely new class of drugs targeted for the treatment of
mucociliary disease," said Kenneth Olden, Ph.D., director of
the National Institute of Environmental Health Sciences.
The NIEHS, one of the National Institutes of Health, provided $6.6
million to scientists at the University of North Carolina at Wilmington
and Mount Sinai Medical Center in Miami Beach for the study. The
findings are published in the January issue of the American Journal
of Respiratory and Critical Care Medicine.
Florida red tide consists of microscopic plant-like cells that
produce a potent chemical toxin that causes fish kills, contaminates
shellfish, and creates severe respiratory irritation in people.
As the concentration of red tide increases, waves and wind disperse
toxin particles into the air, causing irritation of the eyes, nose,
throat, lips and tongue.
After identifying the most potent of the red tide toxins, researchers
asked a second question: Can the respiratory problems caused by
the toxin be prevented? Their research led to the discovery of two
"anti-toxins" a man-made compound known as ß-Naphthoyl-brevetoxin,
and brevenal, a natural compound produced by the organism itself.
Experiments conducted in sheep revealed that both compounds were
able to block the effects of the red tide toxin on the respiratory
While conducting experiments on the red tide anti-toxins, researchers
made an even more important discovery the anti-toxins behaved
much like drugs used to treat cystic fibrosis. "We found these
compounds are able to speed up the clearance of mucus from the lungs,"
said Daniel Baden, Ph.D., director of University of North Carolina
at Wilmington's Center for Marine Science and director of the project.
According to Baden, mucociliary clearance is one of the most important
defense systems in the lungs, protecting the airways from bacteria
and pollutants. "We think the ability of these anti-toxins
to improve the clearance of mucus may be due to a combination of
increased movement of the cilia, the tiny hair-like structures that
line the airways, and a thinning of mucus," he said.
Tests conducted in experimental animals showed these compounds
to be effective at doses 1 million times lower than the current
medications used in the treatment of cystic fibrosis. "These
agents can improve the clearance of mucus, and they may also work
at concentrations that have no side effects," said William
Abraham, Ph.D., a pulmonary pharmacologist at Mount Sinai Medical
Center and author of the study.
"These compounds will serve as experimental models in the
development of drug therapies for those who suffer from cystic fibrosis
and other lung disorders characterized by excessive mucus secretion,"
Cystic fibrosis is the most common fatal genetic disease among
Caucasians. Approximately 30,000 Americans have cystic fibrosis,
and 12 million people carry the defective gene but are not affected
by it. A person with cystic fibrosis produces thick, sticky mucus
that provides a perfect breeding ground for bacterial growth. Cystic
fibrosis patients are susceptible to more strains of bacteria than
others, and have a much harder time fighting these infections.
Symptoms of cystic fibrosis include frequent wheezing, chronic
cough, and pneumonia. While chest thumping is used to clear thick
mucus from the lungs, medications can be given to thin the mucous
and help breathing.