Scientists have a new theory about the progressive, debilitating effects of multiple sclerosis (MS). A recent study published in Science Immunology has revealed that an immune gene can slow down MS progression, putting these cells in the crosshairs as future therapeutic targets.
MS is an autoimmune disease in which the insulating layers around nerve cells called myelin become compromised, affecting their ability to transmit signals. Nearly 1 million Americans are living with MS. They need more effective clinical interventions, especially considering that there is no known cure for MS. The long-term outcomes of the condition are also very difficult to predict.
The scientists from Karolinska Institutet used a mouse model of MS to gain a deeper understanding of the mechanics of degeneration and repair of neural tissue in the condition. Immune cells in the central nervous system called microglia were of particular interest as these are key regulators of these processes. Microglia act as cleanup crews in the brain, removing damaged cells and breaking down their components to be recycled in a process called autophagy.
The scientists silenced Atg7 in the mice, a gene in microglia critical to their function during autophagy. Interestingly, the loss of Atg7 significantly diminished microglia's ability to remove cellular debris around the site of inflammation caused by MS. With microglia being out of action, damaged neural tissue began to pile up, offering scientists an explanation for how MS progresses over time.
Aging mice were also shown to have similar microglia dynamics to the genetically-modified animals that completely lacked Atg7. This data supports the strong correlation between aging and MS progression, of which microglia is evidently playing a central role.
On a positive note, the scientists have proposed therapeutic strategies to boost the action of microglia, thus slowing the condition from advancing.
As lead study author Rasmus Berglund explains: "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."
"By enhancing this process, we hope one day to be able to treat and prevent age-related aspects of neuroinflammatory conditions."