People with multiple sclerosis (MS) gradually develop increasing disability. Researchers at Karolinska Institutet have now found a possible explanation for the progressive course of the disease in mice and how it can be reversed. The study, published in Scientific immunology, may prove valuable for future treatments.
MS is a chronic inflammatory disease of the central nervous system (CNS) and one of the leading causes of neurological impairment.
The disease is usually diagnosed between 20 and 30 years of age. It can cause severe neurological symptoms, such as loss of sensation and tremor, difficulty walking and maintaining balance, memory loss and visual impairment.
MS is a lifelong disease with symptoms that often gradually worsen over time.
In most cases, the disease comes in seizures with some subsequent improvement. However, a gradual loss of function over time is inevitable. Research has made great strides in treatments that reduce the frequency and harmful effects of these seizures.
“Despite these important breakthroughs, the disease generally worsens when the patient has had it for 10 to 20 years,” says Maja Jagodic, associate professor of experimental medicine at the Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet. “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.”
Researchers at Karolinska Institutet have now shown that recovery from MS-like symptoms in mice depends on the ability of the CNS ‘own immune cells – microglia – to break down the remnants of damaged cells, such as myelin.
The processes were interrupted when the researchers removed a so-called autophagy gene, Atg7. Autophagy is a process in which cells usually degrade and recycle their own proteins and other structural components.
Without Atg7, the ability of the microglia to clean away tissue debris created by inflammation was reduced. These residues accumulate over time, which is a possible explanation for the progression of the disease.
The study also shows how microglia from aged mice resemble the cells of young mice lacking Atg7 in terms of deficiencies in this process, which had a negative effect on the course of the disease.
This is a significant result as increasing age is an important risk factor in the progressive phase of MS. The researchers also show how this process can be reversed.
“Plant- and fungal-derived sugar Trehalose restores the functional degradation of myelin residues, stops progression and leads to recovery from MS-like disease.” says doctoral student Rasmus Berglund. “By improving this process, we hope one day to be able to treat and prevent age-related aspects of neuroinflammatory conditions.”
The key identified to improve multiple sclerosis treatment
Rasmus Berglund et al., Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation, Scientific immunologyOctober 16, 2020, DOI: 10.1126 / sciimmunol.abb5077
Provided by Karolinska Institutet
Citation: The study explains the process that exacerbates multiple sclerosis (2020, October 16) retrieved October 18, 2020 from https://medicalxpress.com/news/2020-10-exacerbates-multiple-sclerosis.html
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