A diagnosis of multiple sclerosis (MS) often leaves individuals grappling with uncertainty about the future course of the disease.
Recently, researchers have identified a possible mechanism and treatment target for those most severely affected by MS.
MS leads to nerve cell damage by removing their protective covering, which is crucial for proper nerve signal transmission.
A new study from researchers in the Netherlands indicates that in the most severe MS cases, an immune cell typically responsible for tissue repair and waste clearance becomes overwhelmed with fat droplets.
These cells, known as “foamy microglia”, have been observed in MS patients before, but their exact role was not previously understood.
The latest research suggests they might play a crucial role in the most severe stages of MS.
MS is an autoimmune disorder where the immune system erroneously attacks its own cells, leading to damage through inflammation. The presence of foamy microglia suggests there is more complexity to the disease.
“We found that patients with large numbers of these foamy microglia had a more severe disease course more frequently,” explains molecular physiologist Daan van der Vliet from Leiden University in the Netherlands.
“It does not appear to be simply about the inflammatory response alone.”
The research team examined post-mortem brain tissue from 28 individuals with secondary progressive MS, a stage where cognitive and physical abilities are declining.
This was compared to samples from 10 brains donated by individuals without the disease.
By employing various profiling techniques, the researchers mapped proteins, fats, and active genes in brain regions affected by MS lesions.
These lesions occur when the protective myelin sheath around nerve fibers is attacked by overly aggressive immune cells.
The study found a correlation between the presence of foamy microglia and MS progression, with these cells altering the inflammatory response around lesions by exhibiting a different molecular signature.
Researchers propose that as microglia attempt to repair neuron damage, they become clogged with fats, starting with myelin, which exacerbates inflammation.
“These cells are probably trying to do something good: clearing up damage,” notes van der Vliet.
“But they become overloaded, so to speak. As a result, they can no longer effectively contribute to repair.”
The research also explored a mouse model of MS, where blocking a specific enzyme active in foamy microglia led to improved tissue healing, reinforcing the connection between these immune cells and worsening MS progression.
While still in early research stages, clinical trials in MS patients are necessary to validate the link between foamy microglia and disease progression.
Researchers also aim to study how unrepaired lesions evolve over time.
These findings are promising for understanding why some MS patients remain relatively stable while others experience severe symptoms earlier.
The researchers hope these insights will lead to new MS treatments targeting cellular fat metabolism.
Additionally, this research, alongside other studies, could help identify severe MS cases earlier.
The team discovered fats related to foamy microglia in cerebrospinal fluid, which they suggest could serve as a disease marker.
Related: Scientists Identify Specific Bacteria Linked to Multiple Sclerosis
“That opens the possibility of developing biomarkers in the future that could help doctors identify earlier which patients are at risk of rapid decline – and which treatment would suit them best,” says van der Vliet.
The research has been published in Nature Neuroscience.
