Summary: <\/strong>A collaborative neurobiology study uncovered a cellular mechanism tied to the severe, rapid progression of multiple sclerosis (MS). Published by a multidisciplinary team analyzing human post-mortem brain tissue, the research reveals that accelerated neurological decline is heavily driven by \u201cfoamy microglia\u201d, brain immune cells that become pathologically overwhelmed and structural failures after absorbing excessive amounts of damaged myelin fat.<\/p>\n This discovery shifts the clinical understanding of MS past simple inflammatory models, offering concrete targets for metabolic drug development and predictive spinal fluid biomarkers.<\/p>\n Key Facts<\/strong><\/p>\n Source: <\/strong>KNAW<\/p>\n Researcher Daan van der Vliet, together with colleagues from the Netherlands Institute for Neuroscience, Leiden University, and Utrecht University, has discovered an important mechanism that may be linked to severe progression of multiple sclerosis (MS). In brain tissue from patients with rapidly progressing MS, they found large numbers of abnormal immune cells overloaded with fat droplets. <\/strong><\/p>\n The study offers new leads for treatments as well as biomarkers that could better predict disease progression.<\/p>\n Why does one patient deteriorate rapidly while another does not?<\/strong><\/p>\n In MS, the fatty insulating layer surrounding nerve fibers (myelin) is broken down in the brain and spinal cord. This can lead to neurological symptoms such as difficulties with walking and vision.<\/p>\n MS progresses differently in every patient. Some people live for decades with relatively mild symptoms, while others become severely paralyzed at a young age. Researchers have therefore long tried to understand what causes these differences.<\/p>\n In the new study, the scientists focused on microglia: immune cells in the brain that clear waste and help repair damaged tissue. In MS patients, however, these cells change shape. They become filled with fat droplets, giving them a foamy appearance. Researchers call these cells \u201cfoamy microglia.\u201d<\/p>\n \u201cWe found that patients with large numbers of these foamy microglia had a more severe disease course more frequently,\u201d says researcher Daan van der Vliet.<\/p>\n Cleanup cells that become overwhelmed<\/strong><\/p>\n Under normal circumstances, microglia help clean up damage in the brain. In MS, however, this task may sometimes become too big. The researchers believe the cells absorb so much damaged myelin that they eventually become overwhelmed by their own waste-processing system.<\/p>\n \u201cThese cells are probably trying to do something good: clearing up damage,\u201d Van der Vliet explains. \u201cBut they become overloaded, so to speak. As a result, they can no longer effectively contribute to repair.\u201d<\/p>\n The researchers also discovered that brain inflammations containing foamy microglia behave very differently at the molecular level from MS inflammations without these cells. For example, they contain specific fats involved in chronic inflammatory responses.<\/p>\n A new perspective on MS<\/strong><\/p>\n For a long time, inflammation was thought to be the driving force behind disease progression, but the study also shows that MS may be more complex than that alone. According to the researchers, their work points to a more subtle process.<\/p>\n \u201cIt does not appear to be simply about the inflammatory response alone,\u201d says Van der Vliet. \u201cThese cells are probably attempting to clear damage and promote repair, but that process fails, worsens inflammation, and counteracts recovery.\u201d<\/p>\n Advanced techniques and human brain tissue<\/strong><\/p>\n For the study, the scientists analysed brain tissue from 28 deceased MS patients who had donated their brains to the Netherlands Brain Bank. The team combined several advanced techniques that simultaneously examined gene activity, proteins, and fats within the same MS inflammatory lesions.<\/p>\n According to the researchers, the combination of modern technology and detailed knowledge of brain pathology was especially crucial.<\/p>\n \u201cToday we have incredibly sophisticated techniques that can map the brain in great detail,\u201d Van der Vliet says.<\/p>\n \u201cThe technologies are fantastic, but they tell you relatively little if you cannot connect them to pathology in brain tissue. Precisely because brain tissue has been carefully studied and classified for years by the Netherlands Brain Bank, we were able to recognize these abnormal patterns.\u201d<\/p>\n A possible step toward more personalized treatment<\/strong><\/p>\n In the long term, the discovery may help improve predictions of MS disease progression. The researchers found indications that certain fats associated with foamy microglia can also be measured in patients\u2019 cerebrospinal fluid.<\/p>\n \u201cThat opens the possibility of developing biomarkers in the future that could help doctors identify earlier which patients are at risk of rapid decline \u2014 and which treatment would suit them best.\u201d<\/p>\n In addition, the findings align with ongoing developments in new medicines targeting fat metabolism and chronic lesion expansion in MS. Some of these drugs are already being investigated in clinical studies in collaboration with Roche.<\/p>\n Funding: <\/strong>The research was funded by two Gravitation programs: the Institute for Chemical Immunology (ICI) and the Institute for Chemical NeuroScience (iCNS).<\/p>\n A<\/strong>: It is a classic case of system overload. Microglia enter MS lesions with good intentions: to clean up the fatty myelin debris left behind by autoimmune attacks. However, when the breakdown is too massive, these cells eat far more fat than their internal waste-processing systems can handle. They get bloated into \u201cfoamy microglia,\u201d get stuck, and stop helping with brain repair.<\/p>\n<\/div>\n A<\/strong>: By using advanced, high-definition technology on perfectly preserved tissue from the Netherlands Brain Bank, scientists mapped the exact toxic fats created inside these foamy cell clusters. Because these specific, signature fats leak into the surrounding cerebrospinal fluid, doctors can develop non-invasive spinal taps to spot these destructive markers in living patients early.<\/p>\n<\/div>\n A<\/strong>: Not the wrong problem, but an incomplete one. For a long time, MS progression was viewed purely through the lens of immune-driven inflammation. This study proves that rapid decline is a more complex, subtle metabolic failure. This is exactly why the field is moving toward brand-new drugs, including candidates in clinical trials with Roche, that specifically target fat metabolism to protect the brain.<\/p>\n<\/div>\n<\/div>\n Author:\u00a0<\/strong>Eline Feenstra<\/a>\n
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<\/picture>Key Questions Answered:<\/h3>\n
Editorial Notes:<\/h3>\n
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About this multiple sclerosis research news<\/h2>\n
Source:\u00a0<\/strong>KNAW<\/a>
Contact:\u00a0<\/strong>Eline Feenstra \u2013 KNAW
Image:\u00a0<\/strong>The image is credited to Neuroscience News<\/p>\n