Some of the greatest breakthroughs in scientific research come through serendipity, those accidental discoveries that turn up when we’re looking for something else. A famous example is Alexander Fleming’s discovery of the antibiotic penicillin, which occurred when a previously unknown mold killed a culture of bacteria he was studying.
A similar moment of serendipity in our labs at UNCW’s CREST Research Park may point the way toward exciting new approaches to drug therapy. These could improve the effectiveness of drugs that are not taken up very well by the body. They could also reduce these drugs’ side effects because of the high doses needed to get a therapeutic effect. As so often happens in science, an experiment failed. As my colleague, Andrea Bourdelais, Ph.D., put it, “My work did not work.” But that failure revealed a completely unexpected result for a family of chemicals she was studying.
We call these compounds “Escortins.” That’s because they literally help to escort substances such as anti-cancer chemotherapy drugs into the parts of human cells they need to act on. They can even distinguish between healthy cells and cancerous cells in some instances.
This is important for a several reasons. First, getting a powerful and toxic drug inside a cell means far less of it will be needed to do its job; that can mean far fewer undesired and unavoidable toxic side effects. In the case of chemotherapy drugs, these can include nausea, hair loss and damage to healthy organs.
A second advantage is that these “Escortin” chemicals can even deliver their companion compounds into a precise part of the cell. As Bourdelais explained, “It’s like I’m escorting you not just into a building; I’m taking you to the right room.”
I hasten to say that this is very early work. While these new discoveries have tremendous medical potential, extensive additional research will be needed before we even get to the stage of clinical trials on humans. The experiments we have done so far have shown that chemicals isolated from sea life – such as the toxic algae that produce “red tide” – can offer major benefits to human health. This research is being done by a talented team that includes several members of the UNCW Center for Marine Science faculty, and partners from UNC Charlotte’s department of biology.
So how did an experimental failure lead to that moment of scientific serendipity?
We have been studying a group of compounds called ladder frame polyethers. Those include brevetoxins, which are the chemicals that make the Florida “red tide” deadly to fish. The organisms that produce the brevetoxins also produce beneficial substances, such as the drug brevenal, which has potential to treat cystic fibrosis. Bourdelais was working on methods to figure out how these compounds bind to certain spots called receptors on the surface of mammalian cells. Linking the compounds with fluorescent materials, which glow in ultraviolet light, was a handy way of identifying them under a microscope. Because these fluorescent marker compounds can’t penetrate the cell membrane, they were a good choice for an experiment aimed at finding receptor points on the outside of that membrane.
But when she looked at her samples, she was startled to see that the dyes had done what they weren’t supposed to: penetrate the cell membranes. After the initial disappointment of what seemed like a failure, Bourdelais got to thinking. With her background in pharmacology, she realized that the ladder frame polyether compounds, when linked to the fluorescent dyes, were providing a way for the substances to enter the cells in a way they normally couldn’t. And that this “escorting” effect might work on other chemicals, like anti-cancer drugs, that also have a hard time getting inside cells where they exert their toxic effects.
Luckily, we found some cancer drugs that are nicely fluorescent, which made it easy to see exactly where they were going. We hooked them up with the algae-derived chemicals that we were studying, and sure enough: these newly connected compounds got into the cells much more readily than the cancer-killing drug does by itself. Even better, it turns out that these “escorted” drugs bypassed parts of the cell that would have neutralized or even expelled them. When linked, these combinations are less toxic than the drug itself. To be effective, the drug needs to be released from its “escort” once it reaches the target site. To do that, we developed a special linking molecule that’s cut apart by a specific enzyme.
This has truly exciting implications. That’s because these “Escortin” compounds can help drugs evade the cell’s natural defenses, and because cancer cells have higher concentrations of those link-cutting enzymes than healthy cells do, they are more toxic to the cancer cells than they are to the normal cells. This suggests the potential to create a “pro-drug” that’s toxic just to cancer cells, but not to the whole body. Not only can this mitigate chemotherapy’s debilitating side effects, it can also allow physicians to use much lower doses of very expensive drugs.
Many other researchers are looking at strategies for targeted drug delivery. But most of those experiments involve big, complex molecules like proteins or fats that form a protective coat around their companion chemical. These can be toxic themselves, or cause allergic reactions. The ladder-frame polyethers we’re working with are very small molecules, some of them much more benign in living tissue than the larger complex structures now being used.
Our experiments so far have been in cultures of human and other mammal cells. The next step is tests on animals such as mice, for which we’re seeking grant funding.
UNCW CREST Research Park is a front-runner in marine biotech research and development. Researchers are exploring the potential of natural products derived from the sea to treat or cure human diseases and meet other important needs.
Discover why rising biotechnology and life sciences groups from all over the country are moving to UNCW CREST Research Park. UNCW CREST Research Park offers top-notch commercial laboratories available for lease at affordable rates, flexible terms, and innovative product development opportunities that are unmatched by any other park. Connect with CREST at [email protected] today.
Cece Nunn - Jan 19, 2018
Christina Haley O'Neal - Jan 19, 2018
The Greater Wilmington Business Journal surveyed local economic development groups for updates on their activities....
Spectrum recently launched new offerings for residential and business customers on Bald Head Island....
Bobby Zimmerman has been thinking about opening his own restaurant for years. When the former Pembroke’s space opened in The Forum, he had w...