Drugs Kick-Start MS Repair
Thu, 23rd Apr 2015
Two drugs in common use for skin infections and eczema are also capable of triggering the nervous system to repair damage done by multiple sclerosis (MS), scientists have shown this week.
MS occurs when the immune system attacks material called myelin, which does the neurological equivalent of the insulation found around cables. The resulting damage leads to progressive disability and even paralysis.
Most approaches to managing the disease focus on damping down the immune response to prevent further flare ups, but very little progress has been made in developing therapies capable of repairing the damage done by the disease.
However, writing in Nature, Case Western Reserve University researcher Paul Tesar and his colleagues have developed a test system that has enabled them to screen hundreds of commonly-used drugs. They were looking for any that have the side-effect of encouraging the brain to replace missing myelin, otherwise known as "remyelination".
The team incubated stem cells, called oligodendrocyte precursors, with samples of drugs and then, a few days later, measured the level of a myelin marker. Twenty two agents from an initial screen of over 700 compounds showed promise, of which eleven, when tested in actual cultured slices of brain tissue, were capable of boosting the myelin levels by over 150%.
The top two performers were a skin anti-fungal agent called miconazole, and a steroid chemical known as clobetasol, which is normally used to treat dermatitis.
Administered to mice with the rodent equivalent of MS, these agents produced significant clinical improvements, including, in the majority of the animals, recovery from hind-limb paralysis, which was a common symptom.
"These drugs are switching on stem cells in the brain and turning them into myelin-producing oligodendrocytes, which repair the injury done by the immune system and help the animals to recover from their disability. But we don't know yet how they're doing that," says Paul Tesar. "It's a major focus of our lab work at the moment."
The good news is that because the two drugs uncovered by the study are already licensed for human use, there are fewer regulatory hurdles to overcome in order to test them in multiple sclerosis patients.
"These compounds are licensed for topical use, so we need to explore how they can be administered safely systemically. But we would hope to be able to move them rapidly into the clinic."