Clemson scientist receives NIH grant to pursue drug cure for deadly disease
CLEMSON, South Carolina — Clemson University professor James Morris received a $184,000 grant from the National Institutes of Health to research a new method of starving the deadly parasites that threaten millions of people worldwide.
If successful, the work could lead to the development of oral treatments for African sleeping sickness, Chagas disease and Baghdad boil, an infection that has afflicted U.S. troops in the Middle East.
Morris will lead a multidisciplinary team of scientists from Brigham Young University, the University of Wisconsin, Ohio State University and the University of Kansas to evaluate around 25,000 different molecules that may be able to cut off the parasites from their only source of energy: sugar. Already, Morris and colleagues have developed fluorescent-based sensing technologies that effectively track the glucose that parasites consume from their hosts, giving the researchers insights into cell survival. These parasites must metabolize that glucose in small organelles or tiny sacks called glycosomes.
“We’re going to look for molecules that both inhibit glucose uptake into the cell and then glucose uptake into the glycosomes. We’ll hopefully get both,” said Morris, professor of genetics and biochemistry and a researcher at Clemson’s Eukaryotic Pathogens Innovation Center.
Molecules that show promise will be evaluated as compounds for medicinal drugs.
“You plug the hole, glucose can’t get in and the parasites are going to die of starvation,” Morris said.
Scientists have conducted the genomic sequencing to identify the proteins parasites use to consume glucose from their hosts and have tried, with mixed results, to develop drugs to attack that process. Morris’ effort to inhibit glucose from entering glycosomes is new territory, however. Because humans don’t have these same glycosomes, drugs that target glucose import into these organelles may be more effective and safer to patients, who sometimes die from the current treatments available.
Humans contract these trypanasome parasites from the bite of the tsetse fly, which looks a bit like an overgrown house fly. Trypanosomes are members of the class Kinetoplastea, which caused an estimated 1.4 million cases of disease in 2015, according to the World Health Organization. While these neglected diseases are most prevalent in the underdeveloped countries of sub-Saharan Africa, globalization makes them more of a concern in the United States and elsewhere.
Morris will focus this research intially on Trypanosoma brucei, which causes African sleeping sickness, a fatal disease if left untreated. The disease is opportunistic, with resurgences occurring during civil wars and times of human conflict because disease screening halts and unsanitary conditions prevail. Current therapeutics are often unavailable or difficult to administer in these countries because they are intravenous treatments. At times, treatments can even be fatal to patients.
“We do believe there will be opportunities to treat a couple of other parasites because they all have the same general requirements for food,” Morris said.
Specifically, his work could lead to treatments for Chagas disease, a life-threatening infection that has inflicted 8 million people in South America and has been found in the United States, according to the Centers for Disease Control and Prevention. Morris’ research also could aid in the development of treatments for Baghdad boil, which causes long-lasting skin lesions that don’t heal. Both of these diseases are caused by parasitic eukaryotic pathogens.
The initial two-year funding for Morris’ project comes from the NIH Exploratory/Development of Novel Therapeutics for Eukaryotic Pathogens program that provides an opportunity for three more years of additional funding ($1.8 million total for all five years) if certain research targets are met.
“It’s very prestigious. This is a rare grant mechanism from the NIH that should expedite the discovery of new drugs for eukaryotic pathogens,” said Lesly Temesvari, interim associate dean for research in the College of Science. “Disease caused by eukaryotic pathogens are among the most intractable of all infections. Treatment is often compromised by the availability of few therapeutic options and/or development of resistance. Dr. Morris’s work may lead to important breakthroughs in this area of investigation.”
Clemson’s Eukaryotic Pathogens Innovation Center is an interdisciplinary research cooperative dedicated to advancing the understanding of the molecular mechanisms regulating virulence of eukaryotic pathogens. These eukaryotic pathogens are responsible for an array of deadly diseases, including malaria, amoebic dysentery, sleeping sickness, Chagas disease and fungal meningitis. Since its founding in February 2013, EPIC has secured millions in external research funding, including a $10.5 million National Institutes of Health grant announced in May.
This research is supported by the National Institutes of Health Exploratory/Development Research Grant Award program (R21) under award number 1 R21 AI127575-01 The content is solely the responsibility of the authors and does not necessarily represent the officials views of the National Institutes of Health.