Multiple sclerosis is an autoimmune condition in which components of the immune system mistakenly attack the fatty lining around nerves in the brain and spinal cord. The majority of drugs currently used to tackle the symptoms of MS, therefore, focus on preventing this destruction by targeting the immune system. But a team of scientists think they may have found a different approach to treatment: targeting stem cells already present in the patient’s nervous system.
Photo credit: A 3D rendering of microscopic human nerve cells showing axon dendrites and myelin sheath. 3Dme Creative Studio / Shutterstock
Stem cells, commonly associated with embryos, exist in human adults as well—it is just more difficult to activate them. Stem cells are ‘blank canvas’ cells capable of becoming any type of cell in the body, such as muscle, brain tissue or, in the case of this study, the myelin sheath.
The myelin sheath is a fatty lining around the nerves in the brain that protects and insulates these neural pathways. A sufferer of multiple sclerosis has this protective myelin sheath stripped away, exposing the nerves underneath. These nerves get weathered and damaged without the myelin sheath and, as a result, the patient suffers from shakes and numbness.
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The team, who published the study in Nature, wanted to find a drug that would encourage stem cells in the brain and spinal cord to become the type of cell that produces myelin, which are called oligodendrocytes. With more myelinating cells on board, the damage to nerve cells should slow down, and hopefully further damage will also be prevented. Ideally, the candidate drug would even start to reverse paralysis in multiple sclerosis sufferers.
The two drugs used in the trial were miconazole, which is found in over-the-counter antifungal treatments such as athlete's foot, and clobetasol, which is used to treat skin conditions such as eczema. These might seem like unlikely candidates to coax stem cells to become the important myelin cells in the brain but, of course, there is method behind the madness. The team tested the effects of different drugs (727 to be precise), which all had a history of use in patients, on laboratory-grown stem cells called ‘oligodendrocyte progenitor cells,’ or OPCs for short. Out of all the drugs investigated, the two drugs selected—miconazole and clobetasol—were best at stimulating the conversion of these blank stem cells into myelinating cells.
The effect of these versatile drugs on restoring myelin in the brains of mice with multiple sclerosis-like disease was remarkable. As Robert Miller, a neuroscientist at Case Western Reserve, said: "It was a striking reversal of disease severity in the mice."
Whilst this was very promising with mice, it will be more difficult to evaluate in humans. It is extremely difficult to assess the reversal of brain damage and restoration of myelin reliably in living humans. Another hindrance in the evaluation of recovery is that progress takes a long time. It could take years, not months, to see the effects of myelin restoration, which means that trial studies will take a while and results won’t be quick. However, the team is enthusiastic that they can develop optimized versions of these drugs in the future.
The public are advised not to take the current versions of these drugs to alleviate the symptoms of multiple sclerosis. The forms of drugs being tested have not been refined for the purpose of remylenation yet.