Naegleria fowleri, also known as the brain-eating amoeba, thrives in warm freshwater lakes, ponds and rivers. Though infection is rare, if water containing the amoeba is forced up a person’s nose while swimming or diving, the amoeba can travel to the brain. This will cause primary amoebic meningoencephalitis, an almost always fatal infection that results in tissue damage and hemorrhagic necrosis.
Professor Jim Morris is part of a research group at the Clemson University Eukaryotic Pathogens Innovation Center (EPIC) that has identified a compound that inhibits a key enzyme that brain-eating amoebas need to live.
After reading a 2020 scientific paper from the University of Texas MD Anderson Cancer Center, Jillian McKeon, a postdoctoral fellow in the lab, learned of a compound, HEX, that blocked a critical metabolic pathway in certain types of brain cancer cells. HEX blocked enolase, an essential enzyme involved in glycolysis, which is a series of reactions that extract energy from glucose and is necessary for cell growth.
This information eventually led to the discovery that that inhibitors of sugar metabolism designed to treat brain cancer are toxic to N. fowleri by the Morris Lab.
Morris’ lab tested HEX against N. fowleri grown in the lab and found it was more potent against the amoeba than it was the brain tumor. Researchers tested HEX in an animal model by delivering the compound intranasally, they found that it extended the life of infected rats compared to rodents that did not receive the compound, but it did not kill all the amoeba. Morris said he thinks that it didn’t kill all of the amoeba because they couldn’t keep the level of HEX high enough for long enough.
“The experiments weren’t exhaustive. We didn’t try every dose. We didn’t try combinations with other drugs. But what we showed was that when you put the compound up their noses, it meaningfully extended their lives,” Morris said.
The Morris Lab is working with Jessica Larsen, Carol and John Cromer ’63 Family Endowed Associate Professor in Clemson’s Department of Chemical and Biomolecular Engineering and a researcher at EPIC, who focuses on drug delivery, biomaterials and nanotechnology.
Larsen encapsulated the HEX molecule into a nanoparticle made of polymers, called polymersomes, that can help deliver drugs to the brain. Larsen’s group is researching ways to administer the drug.
“The brain-eating amoeba gets into the brain through the nose, so we’re looking to hijack that route for therapy,” she said.
The hope is the brain-eating amoeba research eventually opens a new avenue of easy at-home or out-of-hospital administration for neural therapeutics.
Detailed findings for the research involving the Morris lab were published in the journal PLOS Pathogens in an article titled “Enolase inhibitors as therapeutic leads for Naegleria fowleri infection.”
Read more in the Clemson News article.
