CMSC INforMS: Neuronal Death Is Possible Onset Source of Multiple Sclerosis
Tuesday, December 15, 2015
Posted by: Elizabeth Porco
The initial trigger for the development of multiple sclerosis (MS) has eluded scientists for decades. Theories have ranged from viral infections to local climate conditions as causative agents in the progression of this neurodegenerative autoimmune disorder.
However now, a team of scientists from the University of Chicago and Northwestern University Feinberg School of Medicine have published results that point to the death of myelin-producing brain cells, or oligodendrocytes, as a possible launching point for MS. The researchers hypothesize that the death of these cells initiates an autoimmune response against myelin, the main hallmark of the disease, which leads to MS-like symptoms in mice.
Interestingly, the investigators were able to prevent the initiation reactions through the application of specially designed nanoparticles, even after the loss of oligodendrocytes. The nanoparticles are being developed for clinical trials that could lead to new treatments in humans.
"Although this was a study in mice, we've shown for the first time one possible mechanism that can trigger MS—the death of the cells responsible for generating myelin can lead to the activation of an autoimmune response against myelin," explained co-senior author Brian Popko, Ph.D., professor of neurological disorders at the University of Chicago. "Protecting these cells in susceptible individuals might help delay or prevent MS."
The findings from this study were published recently in Nature Neuroscience through an article entitled “Oligodendrocyte death results in immune-mediated CNS demyelination.”
The Chicago scientists genetically engineered a mouse strain that allowed them to target oligodendrocytes, in order to study their hypothesis of how MS is triggered. When the researchers specifically killed oligodendrocytes, they observed MS-like symptoms that affected the ability of the mice to walk. After this initial event, the central nervous systems of the mice regenerated their myelin-producing cells, enabling them to walk again. However, roughly six months later, the MS-like symptoms quickly reappeared.
"To our knowledge, this is the first evidence that oligodendrocyte death can trigger myelin autoimmunity, initiating inflammation and tissue damage in the central nervous system during MS," noted lead author Maria Traka, Ph.D., research associate professor in the department of neurology at the University of Chicago.
For the moment, the researchers are unsure if there are specific causes for oligodendrocyte death in MS patients, as various factors can lead to neuronal death, such as developmental disorders, viral infections, and even environmental pollutants. Yet, the scientists feel that it is possible MS could develop years after an initial injury to the brain that triggers oligodendrocyte death.
The research team’s mouse model also allowed them to test new drugs against progressive MS. In particular, they developed nanoparticles that created tolerance to the myelin antigen when administered and prevented progressive MS from developing.
"We're encouraged that immune tolerance induced with nanoparticles could stop disease progression in a model of chronic MS as efficiently as it can in progressive-remitting models of MS," remarked co-senior author Stephen Miller, Ph.D., professor of microbiology-immunology at Northwestern University Feinberg School of Medicine, who’s laboratory developed the nanoparticle technology.
Dr. Popko added that "protecting oligodendrocytes in susceptible individuals might help delay or prevent MS from initiating. It's likely that therapeutic strategies that intervene early in the disease process will have a greater impact."
The researchers are energized to continue their study into the underlying molecular mechanisms that lead to the initial first step of MS. Additionally, they are looking forward to beginning human clinical trials with the nanoparticles.
“It will be exciting to determine the nature of this process in humans—its precise role in MS and whether therapies to prevent it are effective," said Dr. Popko.
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