Multiple sclerosis is an often debilitating autoimmune disease characterized by muscle weakness, vision problems, impaired coordination, and physical numbness. Currently, treatments for this disease focus on managing the symptoms, but what if we could tackle their main cause in the brain?
Although the root causes of multiple sclerosis (MS) remain unknown, we do know that one factor for its symptoms is demyelination.
During this process, the immune system attacks and damages myelin, or the “coating” around axons, which are the projections that connect nerve cells in the brain and spinal chord.
As a result of this damage, signals transmitted between nerve cells are disrupted, hence the problems with vision, coordination, or muscle control. Therefore, the main challenge for researchers specializing in MS has been how to promote remyelination, which is the creation of a new myelin “sheath,” in an efficient and effective way.
According to a 2016 study, more than 403,600 people in the United States live with MS, while an earlier study pointed to an estimated number of 2.3 million people diagnosed with the condition around the world.
Dr. Veronique Miron — at the MS Society Edinburgh Centre for MS Research in the United Kingdom — and other scientists made a breakthrough in remyelination research when they found that a protein called activin-A plays an important role in the promotion of myelin repair.
At the time, they could not identify the mechanism whereby the protein boosts myelination. But now, Dr. Miron and team have discovered how this protein “switches on” the process of repair.
The researchers’ findings have now been published in the journal Acta Neuropathologica.
Dr. Miron and colleagues studied the myelin production mechanism in which activin-A is implicated both in vivo (using the mouse model of MS) and in vitro (on human tissue provided by the MS Society Tissue Bank).
The scientists found that the processes that led to the production of myelin were dependent on the expression of an activin-A receptor called activin receptor 2a (Acvr2a) on oligodendrocytes, a type of cell able to create myelin.
Looking at tissue samples donated by people who had lived with progressive MS, Dr. Miron and her team saw that Acvr2a levels were significantly higher in nervous tissue that benefitted from remyelination. By contrast, Acvr2a levels were reduced in tissue with no signs of myelin repair.
Activin-A, the researchers also discovered, binds to Acvr2a, signaling the oligodendrocytes to start their work of repair at sites where the axons’ myelin sheath has been damaged.
“When we first discovered this protein activin-A,” Dr. Miron notes, “we didn’t know exactly what role it played in remyelination. We now know it binds to a specific receptor, which then causes cells to carry out myelin repair.”
As remyeliantion is crucial to slowing down the progression of the disease and potentially halting it altogether, Dr. Miron says that the findings of the current study could eventually lead to a new drug target.
“This is a really exciting discovery because [we] can now focus our efforts on developing drugs that target the receptor. If we can do that, we can encourage cells to make new myelin after damage has been done in MS.”
Dr. Veronique Miron
Below, you can watch a video in which Dr. Miron explains the relevance of the study’s findings in the treatment of MS, and how they might point the way to better, more effective therapies.