Combs receives $1.4 million NIH grant for unique Alzheimer’s treatment

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School of Medicine & Health Sciences


GRAND FORKS, N.D. — The National Institutes of Health has awarded over $1.4 million to Professor Colin Combs, Ph.D., chair of the Department of Basic Sciences at the University of North Dakota School of Medicine and Health Sciences, for a unique approach to Alzheimer’s disease treatment. Funding for Combs’s work is supported by a 4½-year, R01 grant from the National Institute on Aging, an institute of the National Institutes of Health. The Research Project Grant (R01) is the original and historically oldest grant mechanism used by the NIH.

Alzheimer’s is the most common type of dementia and affects more than 5 million Americans age 65 and older. It is caused by physical changes in the brain that lead to memory loss and the diminishment of other mental functions necessary for daily life. The disease is estimated to account for 60 to 80 percent of all cases of dementia, according to the Alzheimer’s Association.

“We hope to demonstrate that Alzheimer’s disease can be tracked and even treated by focusing on the intestines,” Combs said. “This type of thinking is in agreement with our understanding of other chronic neurodegenerative diseases such as Parkinson’s disease.”

“As with all of our projects, we pursue them as a team,” Combs said. “I have had two excellent postdoctoral fellows, Dr. Kendra Puig and Dr. Gunjan Manocha, as well as a medical student, Siri Urquhart, working on this project. In addition, we have invaluable clinical collaborators, Dr. Mary Ann Sens, chair of the Department of Pathology at the UND SMHS, and Dr. Ashok Tuteja, an associate professor in the Division of Gastroenterology at the University of Utah, who help to ensure our translational potential.”

In this study, Combs and his team will work to define changes in the gastrointestinal tract compared to the brain during the progression of normal aging and Alzheimer’s disease. They will use a variety of rodent models of Alzheimer’s disease and directly compare these to intestines and brains of human patients who have Alzheimer’s. Their preliminary data suggest that the disease occurs in parallel in both organs with the intestine communicating disease to the brain. This suggests that the UND researchers may be able to alter disease progression in the brain by designing therapeutics strategies that target the intestines first. Combs will be directly testing this idea in mouse models of the disease.

Laboratory mice, Mus musculus to scientists, have been bred for generations to be genetically identical. Because mice are genetically and physiologically similar to humans (mice and humans share 95 percent of their genes), scientists find mice to be incredibly valuable experimental tools for research into the genetic basis of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Scientists have developed a vast knowledge bank of lab mouse DNA that they can use to study how the effect of changes in specific genes may underlie certain diseases.

“Our study will provide insight into whether Alzheimer’s disease can be treated using strategies that influence intestinal functions,” Combs said. “This is counterintuitive to the notion that a drug that treats Alzheimer’s disease needs to get directly into the brain.”