Maresin-1 Molecule Eases Inflammation, Symptoms in Mouse Model
Administering the maresin-1 molecule — a natural anti-inflammatory in the body — in a mouse model of multiple sclerosis (MS) led to lower levels of inflammation and improved neurological function, a recent study showed.
Maresin-1 and other molecules in its family are called specialized pro-resolving mediators (SPMs) and are normally produced in the body to counter inflammation.
However, researchers found that natural levels of these SPMs were significantly diminished — in fact, undetectable — in the spinal cords of the mice and in brain tissue from MS patients. The team thus sought to determine if the administration of maresin-1 would impact disease symptoms.
The findings overall provide “clear evidence that there is inefficient production of SPMs” in MS, the researchers wrote, adding that increasing maresin-1 “minimizes inflammation and mediates therapeutic actions.”
The molecule could be “a novel avenue for the treatment of MS,” the team wrote.
The study, “Administration of Maresin-1 ameliorates the physiopathology of experimental autoimmune encephalomyelitis,” was published in the Journal of Neuroinflammation.
While inflammation plays an important role in the body’s immune response, its excess can lead to tissue damage and cell death. To avoid such damage, the body normally employs several anti-inflammatory mechanisms, including the production of SPMs, to resolve inflammation when it’s no longer needed.
In MS, however, and in other autoimmune conditions of the nervous system, inflammatory responses are uncontrolled and contribute to nerve cell damage and disease progression.
In some inflammatory disorders, like Alzheimer’s disease, it’s been demonstrated that the body fails to produce enough SPMs — which could underlie the rampant inflammation that is observed. While a few studies have suggested a similar link in MS, whether SPMs might be promising therapeutic molecules for the disease remains unknown.
Now, an international team, led by researchers in Spain, sought to unravel this potential relationship.
To do so, they first examined levels of SPMs and the enzymes that help produce them in brain lesions and blood samples from MS patients, as well as in a mouse model of MS.
Overall, levels of multiple SPM molecules were undetectable in MS patient samples as well as in the spinal cords of the mouse model. In patients, this impaired SPM production was linked to low levels of the enzymes that help produce them. In contrast, the production of pro-inflammatory molecules was increased.
Since SPM production appeared to be lacking in MS tissues, the team investigated whether administering the molecules could ease disease symptoms. They chose to test maresin-1 because it was one of the few SPMs that was undetectable both in MS patients and the mouse model. It also is “an understudied member of the SPM superfamily,” the team wrote.
The mice were given one microgram of maresin-1 every day from the time of disease onset, and levels of inflammation were measured at the time of peak disease symptoms. Results showed that the treatment significantly lowered levels of several pro-inflammatory molecules that are known to be involved in MS progression.
It also lowered the accumulation of some immune cell types, including inflammatory T-cells, B-cells, and macrophages in the spinal cord. A lower production of some immune cells also was seen in the blood.
Some types of immune cells can be pro-inflammatory or anti-inflammatory depending on which molecules they release. With maresin-1 treatment, the immune cells that were present in the spinal cord were modulated to be more of the anti-inflammatory type.
For example, maresin-1 promoted the activation, in the spinal cord, of a class of regulatory T-cells that produce an anti-inflammatory molecule called IL-10. Production of IL-10 itself tended to be higher, although not significantly, after treatment.
Macrophages in the spinal cord similarly adopted a more anti-inflammatory state, the researchers said.
Ultimately, these anti-inflammatory effects seemed to translate to reductions in signs of MS disease activity among the mice. Specifically, maresin-1 led to significant protection against neurological impairments, which was indicated by less limb weakness or paralysis. It also prevented the loss of myelin — the protective coating surrounding nerve cells that is lost due to inflammatory attacks in MS.
“Our results suggest that one of the body’s mechanisms for resolving inflammation is not working properly in patients with multiple sclerosis, which could partly explain the episodes of autoimmunity they experience,” Rubén López-Vales, PhD, the study’s senior investigator and a professor at the Universitat Autònoma de Barcelona, in Spain, said in a press release.
The research team added that the findings “indicate that SPMs in general, and [maresin-1] in particular, represent a novel therapeutic avenue for the treatment of MS with promising potential.”