Multiple sclerosis (MS) is a debilitating disease in which the body’s immune system begins attacking itself. This chronic inflammatory disease affects approximately 400,000 individuals in the United States and costs upwards of $10 billion annually. It involves the body’s T cells, or white blood cells, and attacks neurons. Neurons are one of the core components of the body’s central nervous system, which is composed of the brain and spine. These neurons are wrapped with an electrically insulating, protective material called the myelin sheath. The myelin sheath is composed of another type of cells called oligodendrocytes. This outer layer surrounds the axon of the neuron—the portion responsible for carrying a message from one neuron to the next—and is essential for proper transmission of electrical impulses.
In individuals with MS, this myelin sheath is permanently damaged. The destruction of this insulating material results in a wide variety of symptoms, including muscle weakness and spasms, difficulty maintaining balance and coordination, visual problems, fatigue, and sensation changes.
Image Source: Cavallini James
Nature recently published a study that sought to identify drugs that could be utilized for the re-myelination of neurons. In the study, researchers took drugs already determined to be safe by the National Institute of Health (NIH) to test whether oligodendrocyte precursor cells were properly differentiated into myelinating oligodendrocytes in the presence of these supplemental drugs. They identified 22 drugs that increased the formation of oligodendrocytes.
To test whether each drug promoted oligodendrocyte maturation in brain and spinal cord tissue, the researchers obtained slices of mice brains treated with said drug and ranked the drugs on their ability to increase the area of the brain covered with myelin. They uncovered two of the top performing drugs: miconazole, a topical antifungal, and clobetasol, a topical medication made to resemble cortisol hormones, which are vital for maintaining homeostasis.
Researchers then examined whether either of these drugs would increase myelination of neurons in live animals. By generating demyelinated lesions in the spinal cords of mice, drugs were tested during a 10 day period prior to the initiation of remyelination. Essentially, the researchers wanted to see if the drugs could “beat” the body’s natural remyelination response by generating oligodendrocytes earlier. Not only did this work, but they also found that these drugs could enhance myelination in mice without injury or disease.
Once they determined that the drug treatments were reproducible in isolated human stem cells, researchers tested for potential therapeutic effects in mouse models simulating chronic progressive demyelination. Both drugs allowed for functional improvement in the mice, with the majority being able to use one or both back legs.
Interferon, the typical treatment for MS, helps alter brain and spinal cord inflammation in MS patients. Unfortunately, this drug cannot prevent the chronic worsening of MS due to remyelination failures. While the discovery of drugs that may reverse or stop de-myelination is exciting, further studies are needed to optimize the dosage, method of delivery, and chemical structure of the drugs. However, since both drugs that were identified by researchers are capable of crossing into the brain and spinal cord, the initiation of clinical trials seems like a very plausible future step.
