Common Anti-Parasitic Agent Eases Motor Symptoms, Aids Remyelination in MS Mouse Model
A common anti-parasitic agent showed a potential to prevent inflammation and to promote nerve cell recovery — remyelination — in a mouse model of multiple sclerosis (MS).
By promoting the activity of a receptor called P2X4R that is present in microglial cells — immune cells that reside in the brain — ivermectin (marketed as Stromectol, or Soolantra) eased the clinical manifestations of experimental autoimmune encephalomyelitis (EAE; an induced autoimmune disease similar to MS in humans).
Specifically, researchers saw evidence suggesting that ivermectin was “a potential candidate among currently used drugs to promote the repair of myelin damage,” they wrote.
Their discovery was reported in the study “P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis,” published in the journal EMBO Molecular Medicine.
“We are witnessing a discovery that is opening up a new channel of pharmacological development for the treatment of the progressive phase of multiple sclerosis, and with it we want to open a new door on improving the life quality of people who suffer multiple sclerosis,” María Domercq, PhD, member of the Achucarro Basque Center for Neuroscience in Spain and senior author of the study, said in a news release.
Immune cells known as microglia play an important role in brain health. They act as a surveillance system to ensure that no foreign elements do harm to brain cells, and at the same time clear damaged cells from the brain. But if abnormally activated, microglia can promote an inflammatory status that, if allowed to continue for long periods, works to injure the brain by leading to chronic inflammation.
An exacerbated microglial response is known to contribute to MS progression by supporting a damaging inflammatory state.
Researchers at the University of the Basque Country, in Spain, found that the cell surface receptor P2X4R plays an important role in this inflammatory process.
By studying mice with EAE, the team found higher-than-usual levels of P2X4R in microglia cells during acute disease episodes. Samples collected from MS patients showed similar elevated amounts of the receptor.
When researchers blocked P2X4R activity in EAE mice with a chemical inhibitor, disease symptoms progressively worsened. Further tests showed that P2X4R increased inflammation, and prevented nerve cells from recovering the loss of their protective myelin sheath.
Now aware of the importance of P2X4R in regulating both a balanced immune response and in the remyelination process, the researchers examined if strengthening the receptor’s activity might reverse such MS processes as inflammation and myelin loss.
They treated EAE mice with ivermectin, an approved oral medicine widely used to kill parasites — like the worm infections that cause river blindness — because among its many suspected, beneficial capacities is the potential to modulate the activity of P2X4R. [Ivermectin originates from a single microbe discovered in the soil in Japan in 1973.]
The treatment, administrated after disease onset, was found to induce a rapid and significant easing in motor symptoms of the disease. These changes were accompanied by evidence of effective myelin recovery —remyelination — as well as a significant lowering of pro-inflammatory factors and an increase in anti-inflammatory agents.
“The results of our study identify P2X4R as a key modulator of microglia/macrophage polarization, and support the use of IVM [ivermectin] to potentiate a microglia/macrophage switch that favors remyelination in MS,” the researchers concluded.
Because ivermectin “is already used as an anti-parasitic agent in humans,” its approval for testing in clinical trials should be easy to gain, they added.
Theresearchers highlight that these results are only correlative, and other “factors secreted by microglia after P2X4R activation” may also be contributing to the remyelination process. Still, they believe that “manipulating [the] innate immune system to promote repair might be a promising therapeutic strategy for treating MS.”