A study published last Wednesday by UW researchers offers new insight into multiple sclerosis (MS), a disease whose exact cause and cure remain mysteries.
In the study, published in Nature Immunology, Joan Goverman, professor and chair of the department of immunology, along with scientists Qingyong Ji and Luca Castelli, have brought the medical research community one step closer to finding a cure for this disease. The research focused on understanding the pathogenic process of MS.
According to the National MS Society, MS is a chronic disease that attacks the body’s central nervous system (CNS), which is comprised of the brain, spinal cord, and the optic nerves. Within the CNS, nerve cells called neurons constantly send and receive electrical signals that are necessary for normal human functioning. Typically, the signal travels along a “path” called the axon, which is protected by insulation called the myelin sheath. This insulation is essential in ensuring that the signals reach their target.
In a patient with MS, the attack on the CNS causes the myelin protection to erode, forming lesions. This leads to nerve fiber damage, and the “path” along which signals are transmitted is no longer able to function properly. The exact cause of MS remains unknown.
“One of the things that makes MS a very difficult disease to understand is that if you look at 10 patients, each patient will manifest their disease a little bit differently,” Goverman said. “They’ll exhibit a variety of different symptoms that they don’t all share with each other, and that’s largely because these lesions caused by the disease
occur in different parts of the CNS, and nobody understands why they occur.”
Because MS is an autoimmune disease, research focuses on the human immune response, which consists of T cells and B cells. B cells make antibodies, while T cells function either as “helper” CD4 T cells that orchestrate the immune response, or as “killer” CD8 T cells that are responsible for destroying harmful foreign antigens.
“For a century, people have been studying MS with a CD4-based model,” Goverman said. “For a long time, nobody had a model where you could study CD8 T cells, and one of the things that my lab did a number of years ago was to generate a new model that was dependent on the activity of the CD8 T cells.”
This gave the researchers the tool necessary to study the role of the CD8 T cell in MS. CD8 T cells that recognized myelin peptide
were cloned. Then researchers genetically modified mice to express that specific T cell receptor.
“We generated a mouse full of CD8 T cells that recognize myelin peptide, and we also had mice generated the other way, with CD4 T cells,” Goverman said.
Goverman and her team focused not only on the role of the CD8, but closely studied the cell that presents the myelin to the T cell, and found that it can incorrectly instruct the T cell to damage the myelin.
“No one had the tools to look at the cells that are presenting myelin to the CD8 T cells. We’d only just recently developed a model where we could see the CD8 T cells at all, let alone the cell that was presenting myelin to it,” Goverman said.
The study shifted the focus away from solely studying the CD4 T cell, as it has been done for decades, and toward the role of the CD8 T cell in myelin sheath damage. It also shifted focus from only studying CD4 and CD8 T cells to specifically studying the cell that presents the myelin to the T cell.
Although this research is basic rather than clinical, meaning it is not specifically geared toward creating new therapies for MS patients, it is necessary in order to find new treatments.
Edward Clark, professor of immunology and microbiology at the UW, said findings that shed more light on the disease itself — such as those in the new MS study — play a vital role in a possible future cure.
“The more we know about the factors that are contributing to the pathogens, the more leads we have for therapies,” Clark said. “I think that’s exciting.”
However, many hurdles remain in the fight against MS. Annette Wundes, a neurologist and the co-director of the UW MS Center, said recovery from existing damage can be problematic.
“We still have very little to offer in terms of reversing the damage which is caused by MS, so repair is one of the main issues we would like to [tackle],” Wundes said.
Despite this, there have been, and continue to be, important discoveries that have led to improvements, including better strategies to control the disease, and a more interdisciplinary approach to patient care.
“It’s important to realize that we have made huge progress,” Wundes said. “In terms of MS care, we have, over the last few years, [had] a more comprehensive approach, including neurologists, mutation specialists, and psychologists for cognitive disabilities.”
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