Hunting for Clues: Why Some MS Cases Progress Faster than Others
By LIDA TUNESI
When you have multiple sclerosis, your immune system goes after your nervous system. Specifically, it attacks the fatty insulation around your neurons, called myelin, eventually causing nerve damage. For the majority of patients, the clinical course is relatively benign, with some periods characterized by symptoms and others symptom-free. Around 15% of people with multiple sclerosis, in contrast, have the primary progressive form of the disease, or PPMS, meaning their condition gets steadily worse from the outset. The reasons behind this progression remain still largely a mystery, but a new study from the Advanced Science Research Center at The Graduate Center, CUNY (ASRC), provides some new clues for the clinical deterioration detected in those patients.
The study from the laboratory of Professor Patrizia Casaccia, founding director of ASRC’s Neuroscience Initiative, appears in Scientific Reports. Researchers Mario Amatruda, Maureen Wentling, Benjamin Inbar, and Kamilah Castro were co-authors of the paper.
The researchers looked for lipids that are present in different amounts in the blood of MS patients with rapid clinical deterioration, and those present in the blood of patients with a more stable and slower disease course. Lipids are a large group of biomolecules that includes fatty acids, sterols (including cholesterol), and sphingolipids. More research on the identified lipids could help researchers figure out the mechanisms behind the disease.
The scientists took blood samples from people without MS, individuals with rapidly progressing PPMS, and those with less rapidly progressing PPMS. Their work turned up three differentially abundant lipids: a sphingomyelin, a mono-hexosylceramide, and lyso-phosphatidic acid. The first two were present at higher levels in the blood of PPMS patients compared to healthy volunteers. This reflected the extent of myelin damage since sphingolipids are components of cell membranes including that of myelinating oligodendrocytes. The third lipid, lysophosphatidic acid, showed up in different amounts in rapidly versus slowly progressing PPMS patients.
Since this lipid does not have a structural role, but rather exerts a signaling function in cells, it is an exciting finding which may allow for a better understanding of the processes underlying clinical deterioration. The new study provides further support to the concept that lipid metabolism is critically involved in multiple sclerosis progression, a finding warranting further future research. Together with previous studies from the same group, this publication highlights the importance of studying lipid mediators to better understand the mechanisms leading to aggressive disease course in MS, with the goal of identifying potential therapeutic strategies.