March 16, 2015
By Whitney L.J. Howell
Think about the ocean, and visions of whales, shellfish and the occasional starfish might pop to mind, not medical therapeutics and advancements in drug delivery. But with new research, the waves that crash on North Carolina’s coast are bringing innovative strategies and tools for improving health.
Together, researchers from the University of North Carolina-Wilmington and East Carolina University’s Brody School of Medicine are investigating how microorganisms found in ocean waters could improve the performance of existing medications, such as drugs for diabetes, cancer and heart disease.
“There’s a new class of compounds based on marine life that can get inside cells and show the cell’s permeability,” said David Brown, an ECU cardiac physiologist and associate physiology professor involved in the partnership.
Brown said UNCW researchers know the ocean side of the equation, whereas his group has studied compounds that can potentially be used to create designer medicines that get into cells and function better.
“Where UNCW’s expertise stops … is where we pick up,” he said.
The partnership, which still awaits final funding approval, formed in response to a call from the University of North Carolina Board of Governors for game-changing research between UNC system institutions that could spawn new approaches to treating disease.
Sharing work & benefits
Any research successes borne from North Carolina’s 300 miles of coastline and estuaries would likely be further supported by the UNCW-based Marine Biotechnology in North Carolina program and the nonprofit Wilmington-based Marine Bio-Technologies Center of Innovation. The Bio-Technologies Center, bolstered by a $2.5 million grant from the N.C. Biotechnology Center, is charged with helping shepherd discoveries into products and processes.
UNCW Center for Marine Science Director Dan Baden, Ph.D., with some of the more than 750 cloned samples from more than 500 microorganisms collected from the waters off North Carolina’s coast.
The marine life component of this collaboration comes from the lab work of UNCW Center for Marine Science director Dan Baden, who has studied red tide, the algae bloom known for killing large fish populations by paralyzing their central nervous systems.
Baden’s team identified a microorganism capable of crossing a cell’s outer protective layer – the membrane that acts as a gatekeeper, only letting select substances in and out of cells.
His team dubbed these microorganisms “escortins” because they can escort materials through that natural cellular fence, depositing them at a specific target. Escortin™ is already on the market as a cancer-drug delivery tool. Test results showed it delivers cancer medications to cells within minutes, compared to other drug-delivery systems that can take up to a day to be effective.
Work is underway for additional safety and efficacy trials, as well as clinical trials, to test whether Escortin can be used in other ways, Baden said.
Escortin could be given alongside other drugs, said Baden, who is also a UNCW marine sciences professor.
“If we can bind the escortins to a drug of interest at ECU, then we have the potential to develop a pairing where our molecules carry medications across the membrane efficiently,” he explained. He called escortin “a molecular carrier that could potentially have ubiquitous importance well past the end of all our careers.”
Delivering a guarantee
At ECU, Brown’s research has focused on mitochondria, the structures in cells that convert food into energy. He calls mitochondria the key to medication success.
Brown has focused on the mitochondria inside heart cells, how they affect heart disease and irregular heartbeats and how they repair other malfunctioning mitochondria. When cells are diseased, he said, mitochondria don’t work well.
Because of the cell’s outer membrane, there hasn’t yet been a definitive way to get drugs to the mitochondria in order for them to heal and return to normal functioning.
“Many times, there’s no guarantee a medicine will get into the cell that can benefit from it,” Brown said. “There’s no way to be absolutely sure [a medicine] gets to the right place.”
Escortins create that guarantee for mitochondria, Baden said, taking medications through the cell’s outer membrane.
North Carolina waters bring healing
That targeted drug delivery could have a significant impact on adults living near both institutions.
According to 2010 data from the North Carolina State Center for Health Statistics, nearly 13 percent of adults in eastern North Carolina – the highest rate in the state – live with Type 2 diabetes. Data from the Eat Smart Move More NC initiative also revealed between 63 and 68 percent of adults in the same area are overweight or obese.
“Mitochondria in diabetics aren’t good at burning fuel for many reasons,” ECU’s Brown said. “If we can use the ocean to help design treatments, then there’s huge potential for treating the disproportionately high population of diabetics and people with metabolic illness.”
The escortin-medication relationship could also improve the efficacy of heart medications, Baden said. Being able to deliver heart medications to patients who’ve had a heart attack or stroke in a timely manner can potentially decrease avoidable deaths, an important goal in eastern North Carolina, a region known as the “buckle” of the “stroke belt.”
The state’s 300-mile coastline presents the universities with a wealth of discovery opportunities, said Deb Mosca, the Bio-Technologies Center’s chief executive and a microbial geneticist who studies the genetics of microorganisms.
UNCW researchers are already deeply involved in culling the ocean for plants and animals that could benefit human health. Once they find a new organism with intriguing characteristics, they clone it, eliminating the need to harvest more and potentially disrupt the ocean’s ecosystem.
In doing so, Baden said, investigators are looking for new aspects of genetics and chemistry that haven’t been seen before.
Workers in Jeffrey Wright’s lab at UNC Wilmington’s Center for Marine Science examine culturable marine organisms as possible sources of new and important compounds for creating new pharmaceuticals. Photo courtesy: UNC-Wilmington/Jamie Moncrief
“If you combine ECU’s drugs with our molecules, we’ve created new intellectual property that can extend the life of patents and add new value. It’s a scaffold for us to build upon,” UNCW’s Baden said. “Translational science – applying research in a real-world way – earns money from tax dollars and gives back to the American people.”
The process can also work in reverse, he said. If researchers know there’s a need for a certain type of medication that functions in a particular way, they can work toward finding a marine biotechnology solution to the problem. And that could create greater economic stability in the region by bringing new tools, collaborations and science jobs to eastern North Carolina, fueling further economic development.
UNCW is already on that path with its new translational science building, funded by the U.S. Department of Commerce and National Institute of Standards and Technology. The 69,000-square-foot space is the first of its type in the region, and it brings together, under one roof, researchers from a variety of scientific fields, making professional cooperations even easier.
“It’s a resource for North Carolina biotechnology, the UNC system and the state that goes beyond just the faculty and institutions working together – it includes students,” Baden said. “It’s about coming into a multidisciplinary, collaborative environment and developing relationships through big science, business and working with the right people to combine expertise and experiences to do things that weren’t possible before.“