Understanding the mechanisms that cause multiple sclerosis may help guide the development of new treatment for progressive multiple sclerosis.
Multiple sclerosis is an autoimmune disease of the central nervous system that involves inflammation-associated damage in the brain that leads to neurodegeneration. Patients with multiple sclerosis may have a relapsing-remitting form, where they cycle between periods of symptoms and no symptoms, or a progressive form, where they experience progressively worse symptoms without any periods of remission. While there are effective therapies to manage relapsing-remitting forms of multiple sclerosis, progressive multiple sclerosis is more difficult to treat. As such, scientists have been dedicating research into discovering a new treatment for progressive multiple sclerosis.
The mechanism behind progressive multiple sclerosis is not yet known
Evidence from previous research suggests that malfunctional neuronal mitochondria – an energy-producing cellular component – are present in the brains of patients with progressive multiple sclerosis. Unfortunately, scientists do not know the underlying mechanism behind this malfunction responsible for progressive multiple sclerosis. In a study published in the journal Brain, researchers from the United States investigated the mechanisms behind progressive multiple sclerosis.
In the study, researchers obtained and analyzed the functional and metabolic qualities of cerebrospinal fluid (CSF) – the fluid that surrounds the brain – from patients with relapsing-remitting multiple sclerosis and patients with progressive multiple sclerosis. The researchers also observed how nerve cells responded to being treated with CSF from relapsing-remitting versus progressive multiple sclerosis patients.
Mitochondrial changes in brain cells cause dysfunction
They found that cells treated with CSF from progressive multiple sclerosis patients developed elongated mitochondria, whereas cells treated with CSF from relapsing-remitting multiple sclerosis patients did not see the same changes. Further, the elongated mitochondria were found to have reduced functioning and were less capable of producing energy, leading to eventual cell death.
The scientists then characterized the CSF to better understand why CSF from progressive multiple sclerosis patients caused these mitochondrial defects. They discovered that CSF from progressive multiple sclerosis patients had increased levels of ceramides. Ceramides cause damage to the mitochondria, thus preventing the cell from producing energy effectively. However, ceramides also led to increased uptake of glucose as a way for the cell to make up for the loss in energy production. By supplementing these cells with glucose, the researchers were able to prevent the damaging effects caused by the CSF.
Understanding the underlying mechanism may be key to discovering treatment
The findings from this study provide valuable information to scientists and their quest to find a new treatment for progressive multiple sclerosis. By having a better understanding of the disease process, scientists may have a better understanding of cellular targets to guide the discovery of new treatment options.
Written by Maggie Leung, PharmD
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Wentling, M., Lopez-Gomez, C., Park, H., Amatruda, M., Ntranos, A., Aramini, J., . . . Casaccia, P. (2019). A metabolic perspective on CSF-mediated neurodegeneration in multiple sclerosis [Abstract]. Brain. doi:10.1093/brain/awz201
Differences in MS patients’ cerebrospinal fluid may be key to drugs that halt progression. (2019, July 15). Retrieved from https://www.eurekalert.org/pub_releases/2019-07/asrc-dim070819.php