Damaged myelin left behind may be more harmful than myelin that’s lostPublished: 06 December 2023 New preclinical research has found that damaged myelin that’s left behind after multiple sclerosis (MS) activity in the body might be more harmful to nerve cells than when it had been completely got rid of. Myelin is the protective fatty coating around the nerve cells which is lost in MS. Previously, scientists believed that the loss of myelin (demyelination) directly led to the degeneration of nerve cell projections, or axons, leaving them vulnerable to inflammatory attacks. The study, conducted using mouse models of myelin-associated disease, found that the failure of microglia, the brain’s resident immune cells, to clear away damaged myelin might be more detrimental to nerve cells than the loss of myelin itself. This discovery is significant because myelin, produced by cells called oligodendrocytes, serves to protect nerve cells from damage, provide nutrient support, and facilitate cell-to-cell communication. In the context of MS, the immune system mistakenly attacks and progressively destroys myelin in the brain and spinal cord. The research suggests that the relationship between immune reactions, demyelination, axon degeneration, and clinical disease is more intricate than previously thought. The study focused on mouse models genetically predisposed to have abnormal or damaged myelin, offering insights into potential mechanisms relevant to MS. The study group, comprised of scientists from across Europe, previously found that immune T-cell-mediated attacks could contribute to axon damage in mouse models. In particular, mice engineered to produce excess proteolipid protein (PLP), a myelin protein, or to have a mutated version of it, exhibited T-cell accumulation and attacks on myelinated tissue. While these mouse models don’t precisely replicate MS, they provide valuable information about potential disease mechanisms. Upon further investigation, the researchers observed an unexpected inverse relationship between demyelination and axonal loss. In simpler terms, nerves with damaged myelin were more likely to continue degenerating compared to nerves where the damaged myelin had been effectively removed. The presence of small axonal spheroids, indicative of progressing neurodegeneration, was more pronounced in the model where most axons remained myelinated over time. The findings challenge the conventional understanding of the role of myelin in MS-related neurodegeneration, suggesting that damaged myelin might have a more detrimental impact on nerve cells than previously believed. This research opens new avenues for exploring the intricate interactions between abnormal oligodendrocytes, microglia, and immune responses in the context of MS, potentially offering novel insights for future therapeutic strategies. Other Stories You May Be Interested In... News Study finds people with MS may have increased risk of cancer View article News Novel drug slows disability progression in SPMS View article News Study found Ocrevus and rituximab may not slow disability progression in PPMS View article