OREGON STATE UNIVERSITY

Scientists discover "pond scum" yields potent compounds

12/19/2000

CORVALLIS, Ore. - A team of scientists has discovered an extremely potent neurotoxin in marine blue-green algae - essentially "pond scum" - that has the potential to lead to new treatments for pain, epilepsy and neurodegenerative disorders.

The compound is called "kalkitoxin," named after Kalki Beach on the island of Curacao from which it was harvested. The findings were announced today at a major international conference in Hawaii hosted by the American Chemical Society.

William "Bill" Gerwick, a professor of pharmacy at Oregon State University and principal investigator in the study, said kalkitoxin is so potent that a half-drop of the compound could kill an entire swimming pool of animal-derived nerve cells, or neurons.

"Its potency is tenfold stronger than saxitoxin, which periodically shuts down some of the shellfish harvesting along the Northwest coast," Gerwick said.

Kalkitoxin has a complex, three-dimensional structure with five "stereo centers" - each one of which is an asymmetric arrangement of atoms about a carbon atom, and is the hallmark of a biologically active molecule from nature. The structure results in a sophisticated system that associates with enzymes, nerve-cell receptors and other molecules.

Though kalkitoxin's purpose in blue-green algae is unclear, its target appears to be sodium-ion channels, which are pores within the membranes of neurons that serve as voltage gates. These gates are the primary means by which neurons build up an electrical charge.

"Kalkitoxin appears to block the sodium channels, preventing the nerve cells from firing off their electrical signals," Gerwick said. "That is the same process that some drugs, including topiramate, have in helping to suppress epileptic attacks."

Some painkillers, such as lidocaine, also work by blocking sodium channels.

"The potential is there for selectively activating or blocking these sodium channels to treat neurodegenerative diseases," Gerwick said. "Even if kalkitoxin does not become a useful pharmaceutical itself, it is a valuable tool to understand how the channels work and how disease and drugs affect them."

Gerwick's research team has been collecting algae samples from tropical locations around the world to study them for their pharmaceutical properties. Nearly a decade ago, they harvested a microalga known as "Lyngbya majuscula" near Curacao - an island off of Venezuela - and later identified a compound within the alga called Curacin A that had anti-cancer properties similar to taxol.

In this latest study, the OSU researchers looked at samples of "Lyngbya majuscula" that were from other bays on Curacao. They were surprised to discover that while various samples of algae appeared nearly identical, they were markedly different chemically and biochemically.

"There is a pronounced difference in the natural products that different strains make," Gerwick said. "It isn't clear whether we lack an understanding of the species concept as applied to these algae, or if these blue-green algae are actually the same species but represent different chemical races.

"Regardless, they offer a treasure trove of natural products that may have real scientific and pharmaceutical value," he added.

Gerwick said the potency of kalkitoxin does make it a candidate for possible pharmaceutical use. "Its incredible potency means that it is binding with greater affinity," he pointed out. "When that happens, there always is a chance that you can have greater specificity of drug action."

Though some of the most promising "Lyngbya majuscula" samples that have yielded both kalkitoxin and Curacin A have come from Curacao, other locations also have been fruitful. Gerwick's OSU research team has found promising algae samples near Madagascar and Fiji, while University of Hawaii researchers report similar findings from Guam.

Curacao remains a favorite for Gerwick, however.

"Kalki Beach is such a spectacularly beautiful place, and fairly isolated," he said. "To think that such a promising compound comes from what essentially is pond scum is ironic. It is a great example of the old saying, however, that one person's garbage is another person's treasure."

Gerwick's recent research was funded by the National Institutes of Health, Dow AgriSciences and Oregon Sea Grant.

Findings of the research were presented at the 2000 International Chemical Congress of Pacific Basin Societies in Hawaii. It is sponsored by the American Chemical Society in conjunction with its counterparts in Australia, Canada, Japan and New Zealand.