JUL 17, 2019 9:02 AM PDT

The Composition of Cerebrospinal Fluid in MS patients Could Be The Key To Treatments That Halt Progression

WRITTEN BY: Nouran Amin

The range of disability for individuals living with multiple sclerosis (MS) varies significantly depending on the relapsing/remitting form of the disease. However, when MS patients experience periods of clinical remission, or the progressive form, they will continue to have neurological deterioration. Present therapeutics are effective but only for relapsing/remitting MS--treatment for progressive MS remains a challenge.

NeuroscienceNews.com: The top portion of this graphic features Neurons (blue) with axons wrapped by normal myelin (yellow). The lower portion of this graphic illustrates neurons with pathological axons wrapped by damaged myelin (yellow and pink). The elongated mitochondria (purple) in the lower portion are dysfunctional and characterized by accumulation of toxic ceramides (green). The image is credited to Jeremy Weichsel at Biovisioning.

Now researchers are asking if there are potential mechanisms that may be examined or targeted for possibly new therapeutic developments. Earlier studies explored neuronal mitochondrial dysfunction because it was found to occur in the brains of MS patients with progressive clinical disability. However, these studies could not determine the molecular mechanisms that may be targeted for treatment.

Recently, a study published in the journal Brain explains how researchers from the Advanced Science Research Center (ASRC) at The Graduate Center, CUNY and Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai have pinpointed potential mechanisms that may inform the new therapeutic developments for the effective manage of progressive MS.

"Because the brain is bathed by the cerebrospinal fluid (CSF), we asked whether treating cultured neurons with the CSF from MS patients with a relapsing/remitting or a progressive disease course would possibly elicit different effects on neuronal mitochondrial function," said the study's primary investigator Patrizia Casaccia, Einstein Professor of Biology at The Graduate Center and founding director of the Neuroscience Initiative at the ASRC. "We detected dramatic differences in the shape of the neuronal mitochondria and their ability to produce energy. Only exposure to the CSF from progressive MS patients caused neuronal mitochondria to fuse and elongate while rendering them unable to produce energy. We therefore searched for potential mechanisms of CSF-induced neurodegeneration with the intent to define therapeutic strategies."

Learn more about the progressive form of MS:

"When we exposed cultured neurons to ceramides, we elicited the same changes caused by exposure to CSF from progressive MS patients, and we further discovered that ceramides induced neuronal damage by acting on two cellular mechanisms," said Maureen Wentling, a research associate in the Casaccia lab and the study's first author. "On one end, ceramides impaired the ability of neurons to make energy by directly damaging the mitochondria. On the other end, they also forced neurons to more rapidly uptake glucose in an attempt to provide energy for the cell."

Source: Science Daily

About the Author
Doctorate (PhD)
Nouran is a scientist, educator, and life-long learner with a passion for making science more communicable. When not busy in the lab isolating blood macrophages, she enjoys writing on various STEM topics.
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