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People with multiple sclerosis (MS) gradually develop increasing functional impairment. Researchers at Karolinska Institutet in Sweden have found a possible explanation for the progressive course of this disease in mice and how it can be reversed. The analysis, which is published in Science Immunology, can prove beneficial to future treatments.
MS is a chronic inflammatory disease of the central nervous system (CNS) and a few of the main causes of neurological functional impairment.
The disease is usually diagnosed between 20 and 30 years old. It can cause severe neurological symptoms, such as loss of feeling and trembling, difficulties walking and keeping balance, memory failure and visual impairment. MS is a lifelong disorder with symptoms that most often slowly worsen over time.
Worse with aging In the majority of cases the disease comes in bouts with a certain amount of subsequent retrieval. A gradual loss of function with time is, however, inevitable. Research has made amazing progress in treatments that decrease the frequency and damaging effects of these bouts.
Researchers at Karolinska Institutet have now shown that recovery from MS-like symptoms in mice is dependent on the ability of the CNS’s own immune cells – microglia – to break down the remains of damaged cells, such as myelin.
Despite these important breakthroughs, the disease generally worsens when the patient has had it for 10 to 20 years. There is currently only one, recently approved, treatment for what is called the secondary progressive phase. The mechanisms behind this progressive phase require more research.”-Maja Jagodic, docent of experimental medicine at the Department of Clinical Neuroscience and the Centre for Molecular Medicine, Karolinska Institutet
The procedures was interrupted when the researchers removed a so-called autophagy gene, Atg7. Autophagy is a process where cells normally break down and recycle their own proteins and other structural components.
Without Atg7 the ability of the microglia to clean away tissue residues generated by the inflammation was reduced. These residues accumulated over time, which is a possible explanation for the progressiveness of the disease.
The study also shows how microglia from aged mice resemble the cells from mice that lacked Atg7 in terms of deficiencies in this process, which had a negative effect on the course of this disease.
Preventing the development of MS This is a significant result since increasing age is a significant risk factor in the progressive period of MS. The researchers also show how this procedure can be reversed.
“The plant and fungi-derived sugar Trehalose restores the functional breakdown of myelin residues, stops the progression and leads to recovery from MS-like disease.” Says doctoral student Rasmus Berglund. “By enhancing this process we hope one day to be able to treat and prevent age-related aspects of neuroinflammatory conditions.”
Karolinska Institutet
Berglund, R., et al. (2020) Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation. Science Immunology. doi.org/10.1126/sciimmunol.abb5077.
