Approved Corticosteroid Medrysone Prompts Myelin Repair in Mice
Mice treated with medrysone saw increases in oligodendrocyte activity, myelin basic protein levels
Treatment with medrysone, a glucocorticoid approved in the U.S. as a topical treatment for certain inflammatory eye diseases, improved repair of myelin in a mouse model of demyelination, a new study shows.
The results suggest medrysone may be a useful treatment for multiple sclerosis (MS), which is caused by inflammation that damages the myelin sheath in the brain and spinal cord.
The study, “Myelin repair is fostered by the corticosteroid medrysone specifically acting on astroglial subpopulations,” was published in eBioMedicine.
The myelin sheath is a fatty substance that wraps around nerve fibers and helps them send electrical signals. In MS, abnormal inflammation damages myelin, interfering with normal nerve signaling and ultimately leading to disease symptoms.
When myelin is damaged, it can be repaired in a process called remyelination — but in people with MS, especially in the disease’s later stages, this process is inefficient. While MS therapies are able to dampen the inflammation and slow disease progression, none can promote remyelination and potentially restore lost function.
Prior experiments using cell models suggested medrysone can activate oligodendrocytes, the cells mainly responsible for making new myelin in the brain. Here, scientists at Heinrich-Heine-University tested this corticosteroid’s effects in a mouse model of myelin loss, which was induced by putting a toxic compound called cuprizone in the mice’s feed.
Analyses of the mice’s brains showed that, in untreated mice, cuprizone led to marked myelin loss, as expected. By comparison, mice treated with medrysone saw a significant increase in oligodendrocyte activity and in levels of myelin basic protein (MBP), a major component of the myelin sheath.
Numbers of nodes of Ranvier — structures formed by a healthy myelin sheath — also increased in mice treated with medrysone, reaching levels similar to normal within a week of stopping cuprizone.
“We here describe that medrysone application in vivo [in living animals] promotes myelin repair activities in a chronic demyelination set-up,” the researchers concluded.
The research team also noted medrysone appeared to improve body weight for mice on cuprizone, which indicated better overall health. Collectively, the finding “suggests that this drug may be of use as a potential treatment for late-stage MS,” the scientists wrote.
Contrary to previous findings, in this model, researchers saw little evidence that medrysone directly affected oligodendrocytes. Instead, the glucocorticoid acted mainly on astrocytes, star-shaped cells that perform a range of activities to help support neuronal function.
An astrocyte-driven inflammatory response called astrogliosis has been implicated in myelin loss, but astrocytes are also essential for removing damaged myelin to clear the way for remyelination. In a battery of experiments, the researchers showed medrysone generally reduced astrocytes’ damaging inflammatory activity, while enhancing their repair-related functions.
“Medrysone application … reduced numbers of neurotoxic-like astrocytes … while it simultaneously enhanced cell numbers with a neuroprotective character,” the scientists wrote.
The researchers called for further study of medrysone, noting its effects in MS models and human cells should be investigated.
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