Could our genes hold the key to unlocking the mystery of multiple sclerosis? The National Institutes of Health (NIH) is betting on it. They have awarded a $1.9 million grant to Benaroya Research Institute (BRI) at Virginia Mason Medical Center to look for changes that take place at the molecular level in immune cells responsible for the damage caused by multiple sclerosis (MS).
The co-principal investigators are Steve Ziegler, Ph.D., a member of BRI and Director of the Immunology Research Program, and Estelle Bettelli, Ph.D., an assistant member of BRI.
“We want to understand the factors that make these cells target the spinal cord and brain to cause disease," said Bettelli in a press release. Bettelli and other scientists have identified different types of T cells, which they believe induce MS and other autoimmune diseases. She has also developed system models to study different forms of multiple sclerosis.
"This work highlights a key mechanism for understanding and modifying the immune cells that cause autoimmune diseases like MS," said BRI Director Gerald Nepom, M.D., Ph.D., in the press release. "It is an exciting example of the power of merging new genomic technologies with state-of-the-art immunology research to address a major clinical need."
Biobank: A Wealth of Information
The researchers will study samples from BRI’s Multiple Sclerosis and Healthy Control Biorepositories. A biorepository, or biobank, contains blood and tissue samples collected from people with a specific condition, as well as samples from healthy volunteers.
“Biorepositories are used to better understand the biomarkers associated with the progression of these diseases and identify targets for new therapies," explained Ziegler and Bettelli in an interview with Healthline. "BRI is unique in having such a rich and broad group of biorepositories for our research.”
The scientists will isolate white blood cells called CD4+ T cells, which are thought to cause and exacerbate MS. They will use a technology called DNase hypersensitive site analysis to map regulatory regions in the genome, which is a person's complete set of genetic information, consisting of 23 pairs of chromosomes.
“These regulatory regions control the expression of genes in specific cell types," Ziegler and Bettelli said. "For the studies in this grant, we’re testing the hypothesis that these regulatory regions will be different in the same cell types in individuals with MS as compared to healthy individuals, and that these differences will drive the inappropriate expression of certain genes in MS patients.”
A Whole New Perspective
Researchers are optimistic that the knowledge gleaned in this study might give scientists a new perspective on MS. Knowing when and where these immune cells are formed in the body is key to learning how to rein in their harmful behavior.
“The understanding of how and which cell populations of the immune system participate in the autoimmune attack is very important for determining current treatments and designing new therapeutics tailored to the different forms of MS," said Bettelli in the press release. "We hope to find ways to significantly inhibit these dangerous cells with new targeted medicines with fewer side effects.”
“In addition," the investigators said, "mapping these regulatory regions may also be useful as a diagnostic tool, especially in the context of tracking the response to therapeutic intervention.”
Even with progress being made to diagnose MS more quickly with magnetic resonance imaging (MRI) scans, patients who suffer a variety of odd symptoms often go from doctor to doctor getting conflicting diagnoses. The first step in treating the disease is to accurately diagnose it as early as possible so that therapy can have the best chance of staving off disease progression.
Even after diagnosis, it is often a process of elimination to find the one disease modifying therapy (DMT) that is most effective for a given patient, while subjecting them to the fewest side effects.
The results of this research could not only help diagnose MS sooner but also pair a patient with a therapy that is genetically matched to their needs for the most effective results.