Several new reports have recently detailed new ways to treat multiple sclerosis (MS), an autoimmune disorder in which the immune system erroneously attacks the insulating shield that surrounds nerve cells, the myelin sheath. The disease causes a host of symptoms including pain, weakness, stiffness, spasms, depression, movement difficulties, and other issues. The cause is still unclear although evidence has recently revealed an associated between the gut microbiome and MS.
A new report in PLOS Biology by scientists at the University of Virginia has found that the aryl hydrocarbon receptor (AHR), which can bind to a variety of molecules in barrier tissues like the gut epithelium, can significantly influence the metabolites produced by the gut microbiome. When AHR activity was blocked in the T cells of a mouse model, a dramatic shift was seen in the production of bile acids and secondary metabolites, which reduced inflammation in the mice. Previous work has also linked AHR to MS.
Though these findings have to be confirmed in people, it could be a way to reduce the flaring inflammation that is seen in MS patients. It may also offer a way to target the microbiome without attempting to use probiotics, which can be difficult to successfully apply to a complex system like a gut microbiome.
An unrelated study in the Journal of Biological Chemistry has identified an unsaturated fat called docosahexaenoyl ethanolamide (DHEA), which could help reduce the symptoms of chronic inflammation, such as what is seen in MS. When a mouse model of MS was exposed to DHEA, the onset of MS was later and when the disease did occur, it was less severe.
The investigators cautioned that more work will be necessary to confirm these findings before they can recommend that people take more fish oil supplements, which contain DHEA. But the researchers are hopeful that this could offer a way to reduce chronic inflammation without relying on medications that may come with side effects.
At the University of California, San Francisco (UCSF), researchers have spent years studying a drug that was originally approved to be an antihistamine, called clemastine, to see if it has a restorative effect on myelin. About a decade ago, the scientists discovered that it stimulated the production of stem cells that make myelin. A trial of the drug showed that in people with MS-induced nerve damage, clemastine could lessen impaired nerve signaling.
Another trial, part of the ReBUILD project, confirmed that clemastine was also working to help repair damaged myelin in the brain. Additional research showed that clemastine acts on myelin. New clinical trials are also planned so that researchers can track the effects clemastine has on myelin more directly.
Another study published in Stem Cell Reports by University of Alberta scientists has used a mouse model of MS to show that fractalkine could also offer a way to repair the myelin damage that occurs in MS.
Cells called oligodendrocyte precursor cells (OPCs) can promote the formation of oligodendrocytes to repair the myelin on neurons. Signaling molecules called chemokines, including a molecule called fractalkine (CX3CL1/FKN) can influence OPCs. When fractalkine was infused into mouse brains after a demyelinating injury, new oligodendrocytes grew and remyelination was observed.
While much of this work remains to be tested in humans, it shows that progress is being made in MS research, and patients may have a variety of treatment options in the coming years.
Sources: PLOS Biology, Journal of Biological Chemistry, UCSF, Stem Cell Reports
