Inhibiting a protein found at high levels in immune cells located in the brain can rejuvenate myelin, the protective coating around nerve cells, according to a multiple sclerosis study in mice.
Blocking the protein, known as the colony-stimulating factor 1 receptor, or CSF1R, can also prevent the immune cells from promoting the inflammation associated with MS, the research indicated.
Argentine researchers presented the findings at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris today. The conference started Oct. 25 and will run through Oct. 28.
Scientists have made great strides in understanding relapsing-remitting multiple sclerosis, or RRMS. And the insight has led to the development of several treatments for RRMS, the least severe form of MS.
Therapies continue to be limited for patients with the three progressive forms of MS, however.
Immune cells in the brain known as microglia play a major role in the destruction of the myelin coating around nerve cells and in nerve cell inflammation, both of which lead to the nerve cell degeneration in multiple sclerosis. This means that finding ways to inhibit microglia may slow the disease’s progression.
Previous studies have shown that CSF1R is essential to microglial cells’ survival and proliferation. In fact, inhibiting the protein reduced microglia activation and brain inflammation in lab and animal models of Alzheimer’s disease and MS, these studies have shown.
An Argentine team wanted to take the research a step further by seeing if inhibiting CSF1R would rejuvenate myelin and prevent neurodegeneration in a mouse model of MS.
The team gave the mice a 0.2% cuprizone diet, which is known to trigger myelin destruction.
Mice on the diet for five to six weeks were able to restore their myelin levels after researchers took them off the diet. Mice on the diet for up to 12 weeks reached a point of demyelination from which they could not recover, however, leading to progressive disability
The team discovered that inhibiting CSF1R reduced demyelination, decreased the number of activated microglial cells, and reduced levels of pro-inflammatory cells in mice that had not reached the demyelination point of no return.
A CSF1R inhibitor failed to help the mice whose demyelination had occurred for up to 12 weeks nearly as much as the other mice. They experienced additional demyelination and less remyelination.
Overall, the results further supported the notion that inhibiting CSF1R can reduce microglial activation and protect neurons from demyelination. They also showed that inhibiting the protein can lead to remyelination.
“Positive results from these experiments could be transferred to the treatment of progressive forms of MS, an urgent and still unmet medical need,” the team concluded.