"We were looking for nasty things in red tide and found this material with potential to do good," said Dr. Daniel Baden, lead investigator and director of the UNCW Center for Marine Science. "This shows the value of ocean and human health research and the potential to discover things not anticipated."
Discovered during a grant funded by a $6.6 million award from the National Institute of Environmental Health Sciences (an institute of the National Institutes of Health), these compounds represent the first potential products to come out of the state's marine biotechnology initiative at UNCW. First awarded in summer 2004, the marine biotechnology funds provide support dollars that allow scientists to develop products, seek patent protection, and move products and technologies to market.
"To have a product in the pipeline in the first year of funding is phenomenal," said Dr. Baden, who thanked Rep. Danny McComas (R-New Hanover) for his leadership in securing this funding for UNCW. "This is truly bench to bedside research. Treatment with these compounds takes effect in about 15 minutes and clears the mucus for an hour or two. Although a drug is years away from being available for humans, aaiPharma is helping UNCW move the product to the next step."
"This is a great return on investment that can be directly attributed to proactive leadership by the UNCW Center for Marine Science," commented Rep. McComas. "The center is at the launching pad to be the greatest marine research facility on the east coast."
In light of the significant therapeutic potential these new classes of compounds provide to the medical community, UNCW entered into an exclusive license agreement with Wilmington, North Carolina based aaiPharma Inc. aaiPharma is a company specializing in providing a full range of development services to the U.S. and international pharmaceutical industry while also developing in-licensed pharmacologically active compounds. For more information on aaiPharma, please refer to its Web site at http://www.aaiPharma.com.
"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. Also collaborating in the NIEHS-funded research is Mount Sinai Medical Center in Miami Beach which provided the asthmatic sheep model. Study findings are published in the January issue of the American Journal of Respiratory and Critical Care Medicine, and the structure of the naturally-occurring drug is published in the Journal of Natural Products December issue.
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 system.
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 Dr. Baden.
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 collaborator on 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," said Baden.
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.
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