Breakthrough Discovery For Cystic Fibrosis Treatment
Air Date: Week of April 1, 2011
Ten years ago, a team of scientists set out to identify the Red Tide toxins that wreak havoc on Florida wild life and residents. Along the way they discovered an antitoxin that is proving to be a promising new treatment for the debilitating pulmonary diseases cystic fibrosis. Dan Baden, lead scientist on the Red Tide study, gave host Steve Curwood all the details.
CURWOOD: There are good news stories and there are bad news stories. This is a wonderful news story. After a decade of study, a team of scientists has discovered tantalizing new information about the mysterious microorganism that causes red tide. Among the hundreds of findings is one that holds promise for people whose lives are cut in half by the disease cystic fibrosis. The lead scientist of the red tide team that made all these discoveries is the Director of Marine Science at the University of North Carolina at Wilmington, Dan Baden.
BADEN: We found twelve different toxins that the organism produces, and this is the Florida red tide dinoflagellate that causes severe bronchial constriction - your nose runs like crazy, you wheeze under worse conditions, and we’ve also found that asthmatics are sometimes very, very sensitive to the effects of these inhaled toxins.
CURWOOD: So you had - at the end of the day, there are just hundreds of findings coming out of this study - how much of it did you think you’d probably find, and maybe the more interesting question is, well, how much did you find that you had no idea?
BADEN: We’ve spoken the last few years within group about the serendipity of this - of finding the things not in search of. The first five years, we found all of these different 12 toxins and had pretty much characterized that they all had little bit different effect and different kinds of potencies in humans.
The second five years, we had run out of toxins, and we said: you know, when the organism lyses, or ruptures, in the environment, anything that’s in that cell gets airborne and gets blown ashore - let’s look for other things. And that’s where we found the antitoxin, produced by the same organism that produces the toxins.
CURWOOD: So tell me, why would an algae produce an antitoxin when it’s about producing these toxins to begin with?
BADEN: Yeah I think the corollary is why does the organism produce toxins in the first place, and it is a subject that is continually being debated by the harmful algae community. We think in this particular case that the molecules may act as regulators, and if the toxin is a regulator for the organism, then the antitoxin perhaps is a modulator of the regulator.
And so the reason that they’re toxic in humans may simply be by blind luck. For all the small molecules in the world made, and all the large target receptors made, some of them are going to interact. And when they interact in a good way, it’s a nutrient; when they interact in a bad way, it’s a toxin.
CURWOOD: So what kind of health benefits did you find?
BADEN: The antitoxin itself, known as brevenal - it promotes a series of physiologic effects known as mucociliary clearance. And the easy way of saying that is it makes your mucus thinner, and it makes it to be expulsed from the lung much more readily.
Put the two together, and it should be a therapy for anything that has thick, ropey mucus that can’t be cleared from the lung. And that is cystic fibrosis and chronic obstructive pulmonary diseases. In our case, our molecule interacts at a new therapeutic site that is unlike any other therapeutic site that’s currently being exploited or treated with any current drug on the market. So a very unique finding.
CURWOOD: How far off are we from using this antitoxin you folks have discovered in red tide to treat people with cystic fibrosis and chronic obstructive pulmonary disease?
BADEN: It’s probably a few years before we’re through clinical phase ones, twos, and clinical phase threes. It can be as long as ten years to get to the final goal. The really interesting thing about this program is that it was funded by the National Institute of Environmental Health Sciences. And this drug, the brevenal, when it finally reaches the marketplace and to patients, will be the first drug to come out of that institute - and that is truly a landmark.
CURWOOD: From the early indications, how effective do you think this proposed medication for cystic fibrosis that you’ve discovered - how effective do you think that is in comparison to present day treatments?
BADEN: It is active at a concentration or a dose known as picograms - ten to the minus 12th grams per dose. That is about a million times more potent than the current therapeutic agents for cystic fibrosis. And so, in fact, coupling new chemistry with new therapeutics and a very potent low concentration needed for efficacy, a lot of side reactions should just disappear.
CURWOOD: Boy, if somebody listening to us who has chronic obstructive pulmonary disease or cystic fibrosis or is close to somebody with these maladies would like to get going with this now, how possible is that?
BADEN: There are some things. First of all, because of the nature of cystic fibrosis, we likely could apply for orphan drug status, which would allow us to move more quickly into clinical trials and entices Big Pharma to get involved a little bit more quickly. And of course finding the pharmaceutical partner to be able to take us to clinical trials - that’s a very expensive undertaking.
CURWOOD: Professor Baden, your team made this amazing discovery after, really - you had ten years of basic research, you answered the original questions but then you went on following other questions…could you get money to do that today, do you think?
BADEN: I think it would be really difficult. In these current economic times, it’s tough to bring program projects of this size - this 15 million dollars to do this work. I’ve seen some writings go across my desk from Congress now talking about holding NIH grants to no more than 400,000 dollars. We wouldn’t even come close to any of the work that we’ve done at 400,000 dollars.
CURWOOD: Dan Baden is Director of Marine Science at the University of North Carolina at Wilmington. Thank you so much, sir!
BADEN: My pleasure, thank you.
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