Dinoflagelettes are fascinating little things. This type of algae has a genome three times larger than a human genome. Some of these organisms make complex neurotoxins that create red tides, killing marine organisms and threatening humans.
But at least one of these algae also makes a natural antitoxin that might be a novel treatment for cystic fibrosis.
The antitoxin in the microorganism responsible for Florida red tides was discovered in 2004. But until now, no one was able to synthesize large amounts of the ladder-shaped toxin known as brevetoxin, or its therapeutic counterpart known as brevenal.
Recently, chemists at the Massachusetts Institute of Technology in Cambridge, Mass. figured out how these toxins are made after more than 20 years of research. Timothy Jamison, who led the team at MIT, said before this discovery making only a few milligrams of these molecules took the equivalent of one person working for a lifetime. Now they can make these pieces in only a few weeks.
“What Jamison has done is very impressive because he has managed to make this core so easily and so efficiently and so specifically,” said John Schwab, a program director at the National Institute of General Medical Sciences, which provided funding for research. “It’s a big advance.”
Daniel Baden, the director of the Center for Marine Science at University of North Carolina, Wilmington, N.C. is using Jamison’s discovery to develop brevenal for cystic fibrosis, and says this is only the beginning.
“I’m really excited about Jamison’s group finding this new way of producing these molecules,” said Baden . “And we’re excited to see how far we can push that.”
Cystic fibrosis is a chronic genetic disease in which the body produces a thick mucus that affects the lungs and digestive system. This mucus clogs the lungs and also blocks the pancreas. Although people are living longer than before, it is an extremely difficult disease to manage.
Baden says brevenal was a serendipitous discovery. Researchers were looking at the different toxins created by the dinoflagellate Karenia brevis. They came across a compound with the same structure as the rest of the toxins, but it seemed to have the opposite effect. While brevetoxin is a lung irritant when inhaled, Baden says brevenal actually restored normal lung function.
Dr. Bill Abraham at Mount Sinai Hospital in New York noticed that this compound “has a lot of the effects that someone would like to see in the reverse of cystic fibrosis,” Baden explained. Researchers at University of North Carolina are developing brevenal in conjunction with the pharmaceutical company AAIPharma, Inc. and hope to begin clinical FDA trials in about a year.
The compound thinned mucus and also stimulated movement of the tracheal mucus. So far, Baden said they have not found a single side effect in animal models. Brevenal is also therapeutically active in a million times lower concentrations than any other cystic fibrosis treatment.
Even more, the applications may not be limited to cystic fibrosis. “We’re nearly convinced now that it’s a new drug target in pulmonary tissues,” Baden said. He says this compound could be used when pulmonary patients no longer respond to one drug. “This makes it incredibly important.”