Two common drugs, one used for alleviating eczema and one used for treating athlete’s foot, may be used in therapies for multiple sclerosis (MS). The drugs have shown promising results in lab and animal studies.
MS is a neurological condition caused by damage to myelin, which is a protein that acts as a protective layer to individual nerve fibers. It causes the body’s immune system to attack the central nervous system (CNS), which is made up of the brain, spinal cord, and optic nerves. When myelin is damaged, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms. The exact cause of MS remains unknown.
“We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis, but until now, we had no way to direct them to act,” said Paul Tesar, PhD, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics, and associate professor in the Department of Genetics & Genome Sciences at the Case Western Reserve School of Medicine. “Our approach was to find drugs that could catalyze the body’s own stem cells to replace the cells lost in multiple sclerosis.”
The study was carried out by researchers from the Case Western Reserve University School of Medicine and other research centers in the U.S., and it was published as a letter in the peer-reviewed scientific journal Nature.
“To replace damaged cells, much of the stem cell field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road,” said Tesar, also a New York Stem Cell Foundation Robertson Investigator and member of the National Center for Regenerative Medicine. “But here we asked if we could find a faster and less invasive approach by using drugs to activate native stem cells already in the adult nervous system and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself.”
Tesar and his colleagues could zero in on the two catalyzing medications only because of the breakthrough that his laboratory achieved in 2011. The researchers developed a process to create massive quantities of a special type of stem cell called an oligodendrocyte progenitor cell (OPC), which are normally found throughout the adult brain and spinal cord. Once Tesar and his team produced billions of these OPCs, they began testing different existing drug formulations which determined if any of the induced OPCs formed new myelinating cells.
The investigators quantified the effects of 727 previously-known drugs on OPCs in the laboratory. The most promising medications were miconazole, most commonly found in antifungal lotions and fungals, and clobetasol, typically available by prescription to treat scalp and other skin conditions. Neither had been considered as a therapeutic for MS, but testing revealed that they each had an ability to stimulate OPCs to form new myelinating cells.
“It was a striking reversal of disease severity in the mice,” said Robert Miller, PhD, a member of the neurosciences faculty at Case Western Reserve who, with Tesar, is a co-senior author of the Nature paper. “The drugs that we identified are able to enhance the regenerative capacity of stem cells in the adult nervous system. This truly represents a paradigm shift in how we think about restoring function to multiple sclerosis patients.”
The drugs have had extraordinary effects on mice, but their impact on human patients will not be known fully until actual clinical trials. In addition to the tests with animal cells, the research team also tested the drugs on human stem cells and saw the medication prompted a similar response to the one seen in mouse cells. Both medications worked well.
“We appreciate that some patients or their families feel they cannot wait for the development of specific approved medications,” Tesar said, “but off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use.”
While MS is the main focus for translating this research into the clinic, a number of other disorders involve myelin loss or dysfunction, including dementia and schizophrenia. Any drugs developed to enhance myelination in MS also hold promise for benefiting these disorders.