The science underlying our understanding of multiple sclerosis — through to new technologies that might expand that understanding in ways “never imagined” — was the focus of a recent educational webinar titled “The Evolving Science of Multiple Sclerosis (MS).”
Kottil Rammohan, MD, a professor of clinical neurology and director of the MS Center of Excellence at the University of Miami Miller School of Medicine, gave the talk.
The April 19 webinar was sponsored by EMD Serono and hosted by John Walsh, MD, the company’s vice president of U.S. Medical Affairs, Neurology and Immunology.
Rammohan began by mentioning the first characterization of MS by Jean-Martin Charcot in the 1800s, and surveyed the variety of failed treatments used on MS patients at different times, including exposure to cold and infection with malaria.
It was not until 1959 that the presence of oligoclonal bands — which indicate local central nervous system production of antibodies — in patients’ cerebrospinal fluid, which bathes the brain and spinal cord, was set as a diagnostic criterion for MS.
Soon afterward, a type of white blood cell known as B-cells or B-lymphocytes (blood cells that produce antibodies) was identified as playing a role in disease progression.
Today, Rammohan said, the picture is much more complex due to the amount of research conducted since 1959, and the known complexity of the disease itself.
He thinks of MS, he said, as having four phases. The first is the immune system reaction against myelin — the protective layer wrapped around neurons that plays a role in transmitting nerve impulses in the brain. Normally, the immune system has a mechanism called tolerance that prevents it from attacking the body’s own cells and tissues. Tolerance to self is lost in this first MS phase, Rammohan said.
Second is the breakdown of the blood-brain barrier — a network of blood vessels and tissue closely spaced that helps keep harmful substances from reaching the brain — allowing immune cells to enter the brain. Some of these cells will specifically target myelin.
The third phase is a second wave of immune cell migration into the brain, while the final phase is marked by brain injury caused by an orchestrated immune response against myelin — orchestrated in the sense that many factors are working together, including crosstalk between B-cells and two other white blood cell types, T-cells and macrophages.
Rammohan pointed out that while the brain injury seen in MS patients is well-characterized, leading to the development of several therapies, and contributing genetic and epigenetic factors known, the actual cause of MS remains a mystery.
He believes that infection by a virus may be the disease’s initial trigger, but how MS continues to progress is not known.
New technology — from genomics, or the analysis of the whole set of roughly 20,000 genes in a person’s DNA, to bioinformatics, the analysis of large amounts of complex biological data — as well as new fields like epigenetics, the study of the suppression and de-repression of genes — all offer the potential to advance disease understanding in ways not previously possible.
Bioinformatics, in particular, will allow researchers to analyze a thousand genes at once, he said, whereas previously they had to be studied individually.
These technological advances, he said, “will allow us to understand the whole system” underlying MS development — an advance he believes will give rise to insights “never imagined.”