The National Institutes of Health has awarded a total of $3.97 million in R01 grant funding to support two new studies on multiple sclerosis (MS), an immune-mediated neurological disorder that impacts approximately 1 million individuals in the United States. Led by Amy Lovett-Racke, PhD, professor of Microbial Infection and Immunity at The Ohio State University College of Medicine, the two studies, “Defining the Role of Molecules Unique to Encephalitogenic T Cells in MS” and “The Role of miRNA Dysregulation on T-cell Differentiation and Function,” will provide new insight into the role of immune cells in the pathogenesis of MS.
Phase One: Investigating Molecules
The first $1.56 million grant funds the study, “Defining the Role of Molecules Unique to Encephalitogenic T Cells in MS,” that began in September 2019. The study is investigating several molecules that may result in being novel therapeutic targets in the treatment of MS.
“These molecules appear to be important in pathogenic T cells in patients with MS, but not in T cells that protect us from infection,” says Dr. Lovett-Racke. “If our study confirms this, then we might have the ability to selectively target the T cells that cause MS, while eliminating the risk of causing unnecessary damage to the T cells that protect us from infection.”
Ohio State College of Medicine collaborators on this grant include Chad Rappleye, PhD, a microbiologist in the Center for Microbial Interface Biology and the Department of Microbial Infection and Immunity; Dan Wozniak, PhD, professor and vice chair of Microbial Infection and Immunity and program director of the Microbial Communities Program Area, Infectious Diseases Institute; Yuhong Yang, MD, research associate professor of Neurology; and Jacob Yount, PhD, assistant professor of Microbial Infection and Immunity.
Phase Two: Developing a Treatment
The second $2.41 million grant will fund the study, “The Role of miRNA Dysregulation on T-cell Differentiation and Function.” This study will analyze micro ribonucleic acid (miRNAs) as potential risk factors in the development of MS, and will explore whether specific miRNAs might be suitable therapeutic targets for more effective treatment of MS. While ribonucleic acid (RNAs) are nucleic acids that exist in all living cells, miRNAs are small RNA that the human body produces naturally to serve as a messenger, carrying information from DNA that controls the synthesis of proteins, which in turn helps to regulate normal gene expression.
“We have identified several miRNAs that are over-expressed in T cells of patients with MS that enhance the development of pathogenic T cells, and amplifies central nervous system, or CNS, inflammation,” says Dr. Lovett-Racke. “This study will determine if modulating the expression of these miRNAs will result in changing susceptibility to CNS inflammation and perhaps provide a novel strategy for treating or even possibly preventing MS.”
Dr. Yang is co-investigator on this study.
Leading the Way
The first study is scheduled to conclude in August 2023, and the timeline for second study is April 2020 through March 2025. Both studies are exclusive to The Ohio State University Wexner Medical Center, and this research is not being conducted anywhere else in the world.