A new system model of multiple sclerosis (MS) that articulates more fully the many complexities of the disease was recently designed by Principal Investigator Estelle Bettelli, PhD, and her team at Benaroya Research Institute at Virginia Mason (BRI). Using the model, scientists can study the disease and how it progresses and look for better therapies and even ways to prevent disease. The model includes several groundbreaking features and studies a factor shown to have an important role in multiple sclerosis. Dr. Bettelli recently received a $2.1 million grant from the National Institutes of Health to further this research.
“We have discovered that the signal transducer and activator of transcription 1 (STAT1) gene, which is a key factor involved in immune system functions, can have a significant impact on multiple sclerosis in our system model,” says Dr. Bettelli. “When we eliminate STAT1, we seem to reduce destructive immune cells and even boost positive ones. This grant will allow us to explore further how STAT1 can be beneficial or detrimental depending on the targeted cell type. If we can learn more, in the future we could determine how to tweak the pathway in the right cell type to protect the cells in the central nervous system.”
The new system model is unique in that it allows researchers to see what is happening in the central nervous system — the brain and the spinal cord — as well as the immune system. Scientists can also see in real time how this pathway affects cells in the brain and the immune system during disease progression. Several disease modifying therapies can modulate STAT1. Dr. Bettelli wants to investigate the mechanisms of STAT1’s protective effect during disease progression and determine how therapies might selectively impact cells in the immune system, the spinal cord and the brain. If some treatments have contrasting effects in the brain and the rest of the body, their efficacy might be more effective by targeting particular cells in the brain, she notes.
“Designing system models of disease is essential,” says Dr. Bettelli, “because we can manipulate and modify one cell type and one gene at a time in our experimental models, which is not feasible in a human, we can control and determine the effect of each variable independently of the others and therefore, we can narrow down on targets for human study. It isn’t a substitute for studying humans, but it points you in the right direction, with much more accuracy, in a timely way. What we do in system models can potentially lead to new translational and clinical studies that impact diagnosis and therapies.”
How BRI Fights Multiple Sclerosis
BRI lab researchers and colleagues discovered a subset of immune system cells which are believed to be potent inducers of MS and other autoimmune diseases. They are studying these cells to determine how to inhibit their harmful function. Researchers have also created models of the four different types of multiple sclerosis for study as well as the new model of MS with the key STAT1 factor.
A recent discovery is potential novel biomarkers of MS that help identify disease activity and could serve as a target for new therapies. Also, BRI President Jane Buckner, MD, along with Virginia Mason Chief of Medicine and MS Clinical Research Director Mariko Kita, MD, and Joan Goverman, PhD, University of Washington, are studying samples of people with MS to understand those who have MS mostly in the spinal cord versus those with disease confined primarily to the brain. This research is being done through biorepositories of volunteers with MS providing blood samples and medical histories.
BRI has five studies that are currently enrolling for different types of MS with a variety of medications and drug delivery systems such as oral medication, injections and infusions. One of the most promising new areas of research lies in remyelination—reversing damage and growing back nerves. BRI and Virginia Mason are now testing a new molecule for the first time in humans that has been shown to repair and reduce lesions.
What is Multiple Sclerosis?
Multiple sclerosis (MS) is an autoimmune disease in which the body’s immune system mistakenly attacks the central nervous system, resulting in symptoms such as numbness in the limbs, fatigue, dizziness, paralysis and/or loss of vision. MS occurs when the immune system attacks myelin — the fatty substance that surrounds and insulates the nerve fibers in the central nervous system. Symptoms of MS will often improve and relapse with time and vary from one person to another. In progressive forms of multiple sclerosis, they gradually worsen. While there are a number of treatments for MS, there is no cure.