Study explains the process that exacerbates MS

Date:
October 16, 2020
Source:
Karolinska Institutet
Summary:
People with multiple sclerosis (MS) gradually develop increasing
functional impairment. Researchers have now found a possible
explanation for the progressive course of the disease in mice and
how it can be reversed. The study can prove valuable to future
treatments.



FULL STORY ========================================================================== People with multiple sclerosis (MS) gradually develop increasing
functional impairment. 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, which is published in
Science Immunology, can prove valuable to future treatments.


==========================================================================
MS is a chronic inflammatory disease of the central nervous system (CNS)
and one of the main causes of neurological functional impairment.

The disease is generally diagnosed between 20 and 30 years of age. It
can cause severe neurological symptoms, such as loss of sensation and trembling, difficulties walking and maintaining balance, memory failure
and visual impairment.

MS is a life-long disease with symptoms that most often gradually worsen
over time.

In the majority of cases the disease comes in bouts with a certain amount
of subsequent recovery. A gradual loss of function with time is, however, inevitable. Research has made great progress in treatments that reduce
the frequency and damaging effects of these bouts.

"Despite these important breakthroughs, the disease generally worsens when
the patient has had it for 10 to 20 years," says Maja Jagodic, docent of experimental medicine at the Department of Clinical Neuroscience and the
Centre 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's own immune cells - - microglia -- to break down the remains
of damaged cells, such as myelin.

The processes 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
created 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
young mice that lacked Atg7 in terms of deficiencies in this process,
which had a negative effect on the course of the disease.

This is a significant result since increasing age is an important risk
factor in the progressive phase of MS. The researchers also show how
this process 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."

========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Rasmus Berglund, Andre Ortlieb Guerreiro-Cacais, Milena
Z. Adzemovic,
Manuel Zeitelhofer, Harald Lund, Ewoud Ewing, Sabrina Ruhrmann, Erik
Nutma, Roham Parsa, Melanie Thessen-Hedreul, Sandra Amor, Robert A.

Harris, Tomas Olsson and Maja Jagodic. Microglial
autophagy-associated phagocytosis is essential for recovery
from neuroinflammation. Science Immunology, 16 October 2020 DOI:
10.1126/sciimmunol.abb5077 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201016143052.htm

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