Harmful or helpful?: Using toxic algae blooms for cystic fibrosis treatment

For such a tiny microscopic organism, the algae behind the Gulf of Mexico’s toxic red tides inflicts a mighty force. Characterized by discolored water, dying marine life, and the release of respiratory irritants, red tides have plagued the Gulf since the 1800s and have since increased in intensity and frequency. Karenia brevis, the dominant algae present in Florida red tides, produces harmful toxins, known as brevetoxins, that cause severe respiratory irritation and neurological effects in humans. Nevertheless, the algae shocked scientists by also creating a chemical with the potential to treat cystic fibrosis.

The initial discovery of the chemical, brevenal, and its abilities was accidental. A team of researchers at the University of North Carolina Wilmington worked to measure the toxicity of different compounds extracted from brevetoxins by exposing guppies to these various samples. Due to a lack of guppies, the team recycled surviving guppies from one treatment to use in treatments with other isolated compounds from brevetoxins. Despite adding a known toxic and lethal compound to beakers with the surviving fish, the guppies surprisingly did not die. The first compound these guppies were exposed to had practically served as an antidote to the harmful effects brought about by red tides. This compound, later coined as brevenal, was found to be a natural brevetoxin antagonist. After further research, the researchers learned specifically how brevenal functions against brevetoxins, by blocking toxins from binding to sodium channel receptors.

Cystic fibrosis, a genetic disease affecting mucus production, works similarly to brevetoxins, also heavily impacting sodium channels. Normally, mucus is thin and slippery, but with cystic fibrosis, mucus thickens, leading to blockage and inflammation in the lungs, pancreas, and other organs. Cystic fibrosis causes increased transportation of sodium across airway linings, and this over-absorption of sodium, alongside defective chloride secretion, draws water away from the airways. These impacts on mucus production, through defective sodium transport, mean that sodium channels are a target for cystic fibrosis drugs.

Researchers at the Mount Sinai Medical Center in Miami, Florida used a model exposing allergic sheep to brevetoxins to compare the beneficial effect of brevenal to that of a different cystic fibrosis drug, amiloride. Both brevenal and amiloride work to block toxins from binding to receptors in the sodium channel. Not only did brevenal prevent the toxin-induced mucus thickening, but it also stimulated mucociliary clearance. Brevenal thinned mucus for easy expulsion by the sheep, confirming the potential of this compound to treat diseases with mucociliary dysfunction. Additionally, low concentrations of brevenal demonstrated the same effect as higher amiloride concentrations. The team’s findings suggest that brevenal is more potent and effective than amiloride.

Silurian Pharmaceuticals, a company based in Oakland, California, has attempted a phase 1 clinical study with brevenal as a treatment for cystic fibrosis. In addition to human use, brevenal may be used on Florida’s endangered manatees. Manatees can both inhale or consume brevetoxins, and this poisoning leads to paralysis and drowning. The Lowry Park Zoo in Tampa, Florida, planned to test brevenal as a treatment on rescued manatees poisoned by brevetoxins, but implementation in the field will take time. A full recovery from brevetoxicosis in manatees typically takes months, so brevenal could accelerate this process.

There is currently no cure for cystic fibrosis, but various treatments have surfaced to control symptoms. Cystic fibrosis can inflict life-threatening symptoms, creating a growing need for successful treatments. While brevenal has demonstrated immense promise, there is still a long way to go before brevenal-derived drugs could be used on humans. Many emerging treatments prove to be unsuccessful, so the continued search for cystic fibrosis treatments is crucial.

Image courtesy of Wikimedia Commons