Environmental Factor, April 2011, National Institute of Environmental Health Sciences
New hope in the treatment of cystic fibrosis
By Ed Kang
"NIEHS has always been very supportive, and we're now at a point where we're going to start giving back," said Baden. "The molecules that we're producing now could treat a multitude of diseases." (Photo courtesy of Steve McCaw)
Fred Tyson, Ph.D., of the Cellular, Organ, and Systems Pathobiology Branch, was the host for the seminar and is the program administrator for Baden's current grant. Tyson noted, "Dan's relationship with NIEHS goes back to his graduate student days." (Photo courtesy of Steve McCaw)
NIEHS-funded scientists recently unveiled the discovery of a potential therapeutic that could dramatically transform the treatment of cystic fibrosis, chronic obstructive pulmonary disease (COPD), and other related lung diseases.
At the March 22 installment of the NIEHS Keystone Seminar Series, Dan Baden, Ph.D., of the University of North Carolina Wilmington (UNCW), chronicled his research that began as an investigation into toxicological mechanisms and has led to the creation of a product with tremendous promise.
The flipside of red tide's toxicological effects
Baden, who has a long-standing relationship with NIEHS, and his team of researchers at the UNCW Center for Marine Science are doing what few, if any, NIEHS researchers have before - parlaying the study of an environmental toxicant into the development of a novel treatment for disease.
Under a grant from NIEHS, Baden has been investigating the toxicological effects of Florida red tide, or Karenia brevis. This extremely toxic microorganism blooms off the coast of Florida annually. It causes fish and marine mammals to die, and when aerosolized by the wind and tide, causes people, even miles inland, to cough, sneeze, and experience other respiratory symptoms.
"Airborne materials from the red tide can cause severe bronchoconstriction at extremely low concentrations measured in only a few trillionths of a gram per cubic meter of air," says Baden.
Trying to uncover the toxic mechanisms for these inhaled particles, Baden's lab has developed the largest Karenia brevis cultivation facility in the country, where they extract component fractions for bioactive materials.
The power of one of those components, brevenal, was discovered when looking for toxicological effects of Karenia brevis in fish bioassays. Lead toxicologist and marine biologist Andrea Bourdelais, Ph.D., observed that some fish weren't dying, despite multiple exposures.
That left her with the hypothesis that the scientists were either working with a fish that was less sensitive to toxic materials or they had uncovered an antitoxin. Within weeks, a subsequent experiment in sheep confirmed that the bronchoconstriction caused by the toxin could be prevented, reduced, or reversed by the antitoxin brevenal at extremely low concentrations.
"The interesting thing is that the toxin and the antitoxin are both produced by the same organism but in different amounts and at different times in the cell cycle," remarks Baden.
From toxic tide to the medicine cabinet
The antitoxin creates a thinner mucous-promoting accelerated removal of particles from the lungs. "Brevenal is effective at a million-fold lower concentration then other therapeutic agents," says Baden. "With brevenal, you can actually turn the bronchial constriction off very efficiently." ��
Baden is embarking on a licensing agreement with a major pharmaceutical firm, and with financial assistance from an NIEHS Recovery Act grant, is hoping to finish preclinical work in 90 days, then move on to clinical trials.
"When a discovery like this is made initially, the hardest thing to deal with are the parents of children with the disease asking when they can get the drug for their child," Baden explained. "That bolsters our need to work faster and do better work to get it to the clinical realm."
But with a new therapeutic target and remarkably high potency, Baden's team's serendipitous discovery could ultimately be a blockbuster drug for those suffering with certain forms of respiratory illness.
(Ed Kang is a public affairs specialist in the Office of Communications and Public Liaison and a regular contributor to the Environmental Factor.)