image: Mohamed Seleem, director of the Center for One Health Research. view more
Credit: Photo by Andrew Mann for Virginia Tech.
The bacterium commonly referred to as C. diff is sometimes called “C-difficult” because it is so hard to treat, said Mohamed Seleem, director of the Center for One Health Research.
Seleem and Nectagen Inc. have received a nearly $275,000 grant from the National Institute of Allergy and Infectious Diseases to study whether synthetic proteins developed by Nectagen can reduce the toxicity of the digestive bacteria.
Deadly diarrhea
The widespread use of antibiotics for a variety of medical issues can destroy beneficial intestinal biomes along with harmful infectious bacteria.
That can open the door for spores of Clostridioides difficile bacteria — known as C. diff — to run rampant in the digestive system, becoming a dangerous pathogen that can lead to life-threatening bouts of intestinal cramps and diarrhea.
Only one new antibiotic drug has been developed to fight C. diff in the past 40 years. Some patients are treated with an antitoxin, but it must be taken intravenously and is often prohibitively expensive.
C. diff recurs in up to 20 percent of patients after treatment, and many of those patients die.
A more effective, less expensive, orally consumable approach is needed to reduce mortality from C. diff.
Academic-private partnership
The grant funding will enable the Seleem Lab in the Center for One Health Research — a collaborative effort of the Virginia-Maryland College of Veterinary Medicine and the Edward Via College of Osteopathic Medicine — to conduct testing on animal models to determine if synthetic “nanoCLAMP” proteins produced by Nectagen, ingested orally, can reduce the toxic effects of C. diff.
“I've done this before with other companies,” said Seleem, the Tyler J. and Frances F. Young Chair in Bacteriology at the veterinary college. “What I love about academia working with a company is that we have the resources, we have the expertise to test a product, to see if the product is ready to move forward to clinical trial.”
The term nanoCLAMP – the prefix “nano” means one-billionth, implying microscopic size, while CLAMP stands for CLostridal Antibody Mimetic Proteins and refers to specialized molecules designed to bind to specific molecular targets within cells.
Nectagen is a Lawrence, Kansas-based biotechnology company that develops and markets “antibody mimetic reagents,” or lab-created molecules that behave similarly to an antibody by imitating an antibody’s binding properties.
“Nectagen is excited to partner with Dr. Seleem to leverage his laboratory's deep expertise in Clostridioides difficile intervention,” said Richard Suderman, research director for Nectagen. “His lab is well positioned to accelerate and guide the development of novel nanoCLAMP therapeutic proteins that neutralize an important C. diff toxin produced during infection.”
Suderman said it is hoped that the nanoCLAMP proteins created by his lab will be “thermally stable and protease resistant” enough to survive in the digestive tract and protect endothelial cells lining the intestines from C. diff toxin damage.
“If you can neutralize these toxins, you just prevented the disease,” Seleem said. “So hopefully, after the C. Diff application, we can move forward to other microorganisms that we can inhibit using this novel technology.”