It’s no secret that eating fish a few times a week is good for your heart. But now North Carolina State University professor of aquatic medicine Ed Noga says tiny proteins he and his graduate student Uma Silphaduang discovered in the gills of a particular fish may lead to a new family of antibiotics.

In search for a better understanding of how hybrid striped bass protect themselves against a slew of diseases in the ocean, the two researchers uncovered and isolated peptide antibiotics produced in the fish’s mast cells, a common immune cell found in all vertebrates. Noga dubbed the antibiotics “piscidins,” stemming from the Latin word for fish, pisces, and launched a startup late last year called Norcarex Bio Corp. with Dr. Oskar Zaborksy to refine the compound and explore its commercial potential for human and veterinary applications. NC State has applied for two patents related to the piscidins and is negotiating an exclusive licensing agreement with Norcarex.

“This is the first time a peptide antibiotic, which is a compound know to have direct toxicity to a pathogen, has been identified and isolated from the mast cells of any animal,” says Noga, who also acts as chief scientific advisor to Norcarex Bio, “which suggests that if fish mast cells have antibiotics of some kind, then maybe it’s true for other vertebrates as well.”

If that’s true, there are some significant implications for humans and how these antibiotics might play a role in combating a number of infectious diseases. Unlike regular antibiotics that target a specific receptor or enzyme, peptide antibiotics can launch a broad attack on a spectrum of organisms such as bacteria, fungi, protozoa, and in some cases even tumor cells and viruses. Their mode of attack makes it difficult for a bacterium to develop resistance, since it would require a major change in its genetic makeup. The growing resistance of diseases to antibiotics is becoming a widespread problem as microbes rearrange their genomes to combat the next generation of anti-microbials.

“They’re really a multi-warhead sort of a defensive chemical in fighting infections,” says Noga. “We have evidence that the piscidins will kill many types of bacteria, including both human and fish pathogens as well as multi-antibiotic resistance isolates.”

Template for new antibiotics?

Norcarex Bio’s most immediate pursuit is the potential use of piscidins as a template for new types of antibiotics. Antibiotics are the third largest pharmaceutical market sector, with worldwide sales of antibiotics totaling $24.7 billion in 1999, including $8.5 billion in the United States. One of the advantages of peptide antibiotics, not just piscidins, says Noga, is that there’s no strong evidence that microbes can develop an acquired resistance to them. But since the compounds don’t have specific targets, there may potentially be more problems with toxicity.

To allay toxicity concerns, Norcarex is initially focused on using the piscidins for a topical agent, such as a cream, to fight external infections in animals and humans, says Zaborsky, co-founder and president of Norcarex Bio. “That’s not to say that there may not be applications for these types of antibiotics for systemic treatments.”

The molecule exhibits interesting features conducive to drug development, adds Zaborsky, who previously served as a program director for the National Science Foundation and director of the board on biology for the National Academy of Sciences. “The bioactivity of the molecule remains even in high salt concentration, so they will not be inactivated as much as other potential compounds. Secondly, the piscidins have good hemolytic properties, so they won’t disrupt red blood cells. With some modifications, we’ll arrive at better molecules.”

“Another important feature is that these compounds are simple in structure … and therefore relatively easy to manufacture,” says Noga.

In search of funding

The two researchers are now on the hunt for seed funding in the ballpark of $500,000, which will enable them to set up an independent laboratory and optimize the efficacy of the natural piscidins, the company’s main lead candidates, by increasing bioactivity and decreasing toxicity. Once key factors of efficacy are demonstrated, Norcarex will be ready for another round of financing, this time in the range of $2 million to $5 million.

But Norcarex doesn’t plan to develop any pharmaceuticals in-house. It’s primarily a research and technology development company that plans to offer novel solutions and compounds to pharmaceutical and healthcare firms. A line of novel peptide antibiotics including piscidins and other peptides from aquatic animals is only one part of Norcarex’s technology portfolio. The success of Noga’s laboratory in isolating and purifying new antibiotics from fish and other aquatic animals provides drug discovery technology to other pharmaceutical companies looking to isolate novel compounds for clinical development. Norcarex will also explore peptide antibiotics within the mast cells of mammals and other organisms, possibly leading to application of these compounds to other diseases.

“Big pharma will be able to push these concepts along much more quickly,” says Noga. “We don’t want to reinvent the wheel.”