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Insights Into Multiple Sclerosis Could Lead to New Treatment

Multiple sclerosis is a neurodegenerative disease with symptoms ranging from limb weakness and tremors to blurred vision. Across the distinct clinical forms of MS, some people experience periods of relapse and remission. For others with a progressive form of the disease, symptoms steadily worsen over time.

In a study in the journal Brain, researchers at the Advanced Science Research Center at The Graduate Center, CUNY, have found a difference in the cerebrospinal fluid of these two groups of patients. These new insights could help scientists develop new treatments for progressive forms of MS.

Authors on the study include research associates Maureen Wentling and Hye-Jin Park, postdoctoral research associate Mario Amatruda, research associate professor James Aramini, and Professor Patrizia Casaccia, founding director of CUNY ASRC’s Neuroscience Initiative. Casaccia has previously investigated connections between body-mass index and MS, and elucidated molecular mechanisms of epigenetic regulation of a known MS drug. Colleagues from the Icahn School of Medicine, Columbia University, the New York Stem Cell Foundation Research Institute, and biotech company BERG also collaborated on the paper.

The researchers put neurons from rats into cerebrospinal fluid from patients with both types of MS, and after some time noticed a difference between the two sets. In the neurons bathed in fluid from progressive patients, the mitochondria had elongated. Mitochondria are little biological machines inside cells that produce the cell’s energy currency, and their lengthening tends to indicate that the cell is under high energy demand. The mitochondria in the neurons bathed with the fluid from progressive patients, however, were not able to keep up with that demand.

The team figured out that the mitochondria’s dysfunction was being caused by high levels of certain types of fatty acids called ceramides. The ceramides were also forcing the neurons to uptake more and more fuel in the form of glucose and lactate, thus depleting their resources.

With these things in mind the scientists tried adding extra glucose and lactate to the spinal fluid at an early stage to see if they could prevent the impairment of neuronal function and promote their survival. It worked, demonstrating that the study could be a first step in finding a way to use this discovery to help patients with progressive MS.

 

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Patrizia Casaccia (Professor, ASRC Neuroscience Initiative Director, Neuroscience) | Profile 1

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