Study Provides New Insights Into Disease Progression

Research Summary: Senolytic treatment diminishes microglia and decreases severity of experimental autoimmune encephalomyelitis

While we now have a number of treatments for multiple sclerosis, there is still a need to better understand what drives disease progression.  If we can improve our knowledge in this area, we will be able to develop more targeted therapeutic options.  In this research article, we are going to summarise a recent study that has identified a potential novel mechanism of disease progression in MS.

What?

Using an animal model of multiple sclerosis (MS), this study looks at the potential role of senescence (described below) in driving disease progression.

Who?

This research was conducted by a team at McGill University in Montreal, Canada.

Where?

The article was published in the Journal of Neuroinflammation.  The full text publication is available here.

When?

The study was published in the journal on November 1, 2024.

BACKGROUND #1: Senescence is a term given to cells that age and stop dividing, but do not die.  There has been a lot of research that has suggested that senescence may be important in neurodegenerative diseases, such as multiple sclerosis.

BACKGROUND #2:  Microglia are part of the immune system that are found in the central nervous system.  They are known to play a role in multiple sclerosis and have also been shown to undergo senescence.

BACKGROUND #3:  The role of senescent microglia in multiple sclerosis is not known.

FINDING #1:  Analysis of microglia from mice with experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis, found that the cells showed signs of being senescent.  

FINDING #2:  A particular genetic marker in these microglia, called BCL2L1 (which is known to encode a protein, BCL-2, that prevents cell death), was found to be closely linked to promoting inflammation and senescence of the cells.  This marker has also been found to be present in higher levels in active lesions of people living with MS, suggesting it may have a role in the disease process.

FINDING #3: The researchers tested a small molecule called Navitoclax or ABT-263, which inhibits the action of BCL-2.  They found that this decreased the amount of microglia present in the spinal cord of mice with EAE and that these mice had improved clinical outcomes.

THOUGHT #1:  The findings of this study are interesting and represent a potential novel avenue of therapeutic intervention in multiple sclerosis.  The fact that they have found a marker that is linked between the animal model of MS and people living with MS is an encouraging sign.

THOUGHT #2: This research is at a very early stage and will require validation in further studies.  If this is successful, this may then progress to looking at clinical trials.  Considering the length of this process, this is still at least 5 years away from being something that could be meaningfully discussed as a therapeutic option.

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