Multiple sclerosis (MS) is an autoimmune condition. In autoimmune diseases, the immune system attacks the body’s own tissues. For people with MS, the attacks are directed at the central nervous system (CNS) — specifically at myelin, a substance that coats the nerves. By damaging the myelin sheath of the CNS, MS can cause such symptoms as muscle weakness, numbness, and vision problems.
What role does myelin damage play in the MS disease course? To learn more about this issue, MyMSTeam talked to Dr. Barry Singer, director and founder of The MS Center for Innovations in Care at Missouri Baptist Medical Center in St. Louis. His award-winning MS website, MS Living Well, started in 2007 and has been a valuable resource in more than 190 countries. He is also the host of the MS Living Well Podcast, including the episode “Remyelination: Repairing Multiple Sclerosis.”
Myelin protects axons in the CNS. Axons are extensions of individual neurons (nerve cells), which allow them to communicate with other cells. Most axons are protected by myelin in the same way that an electrical wire is protected by its coating.
The normal transmission of nerve signals is what allows us to do everything that our bodies do without us having to think about it. That includes such activities as seeing, hearing, and controlling our bodily functions.
Researchers believe that in MS, an abnormal immune system response produces inflammation in the CNS. This inflammation then damages both myelin and oligodendrocytes, the cells that create myelin.
Myelin damage in MS can result in lesions and scar tissue on nerves, which can slow or even stop the nerve signals from reaching the rest of the body. When that happens, MS symptoms can occur.
People with MS most often have a relapsing-remitting disease course, in which they experience periods of new or worsening symptoms, alternating with periods of remission. Another type of disease course is progressive. Progressive MS worsens gradually over time without periods of remission.
Myelin plays an important role in keeping axons healthy. Loss of myelin may make neurons more vulnerable to injury over time, leading to progressive disease. When the axon loss is outpaced by the central nervous system’s ability to compensate for damage, it may prompt the transition from relapsing-remitting MS to progressive MS.
Some disease-modifying therapies (DMTs) have demonstrated an ability to protect the brain from further damage and shrinkage, Dr. Singer said. While a degree of brain shrinkage is an inevitable part of the aging process, brain size can decrease faster in MS. DMTs could help guard against that shrinkage, Dr. Singer noted. DMTs can also prevent new relapses.
“They prevent disability progression over time, so a group of people on a placebo would progress more rapidly than people on a drug,” he said. “They prevent future disease activity.”
While the DMTs show promise, they cannot reverse MS, and people who have lost function due to MS won’t get it back through the use of DMTs, Dr. Singer added. “Unfortunately, these disease-modifying therapies aren't going to bring back old function,” he said. “They are not repair drugs.”
Dr. Singer added that some who take these drugs have difficulty with treatment adherence. Because these medicines won’t lead to a reversal of symptoms, some people assume the drugs aren’t working, and they stop taking them. It’s vital that people with MS understand that these medicines are meant to prevent future damage, not reverse existing symptoms by creating new myelin, he said.
“Unfortunately, we do have patients as they age who have had a lot of disease in their spinal cord or brain, and they start to have cognitive problems and more balance problems,” Dr. Singer said. “They feel like they're getting worse despite treatment — but I think off of disease-modifying therapies, things may be getting worse a lot faster.”
Dr. Singer explained that in addition to taking DMTs, people with MS can do things on their own to keep their physical and cognitive states as sharp as possible. He recommends getting an adequate level of vitamin D, exercising, getting enough sleep, and keeping your mind active — all of which have proven benefits.
“Brain health is really important,” he said. “Exercise has been shown to help keep your brain reserves healthy.”
He also recommended that anyone with MS should quit smoking, which damages both physical and cognitive abilities.
The repair of damaged myelin, known as remyelination, is still being studied in the world's research laboratories and leading MS centers. Dr. Singer said that, while there's nothing ready for FDA approval just yet, significant steps are being made to create effective remyelination treatments for people with MS.
“I've been involved in a number of clinical trials,” Dr. Singer said. “I think we're getting ready to start our sixth clinical trial on myelin repair at my center, and we're working on ways to try to improve remyelination.”
Dr. Singer said the clinical trials in which he’s involved are currently at phase 2. Large phase 3 trials would be the next step if a treatment is proven safe and effective.
“We're looking at antibody therapies [and] oral therapies, so we're hopeful that one day we'll be able to have remyelination treatment,” he said. “In the animal models, you can see when you get these experimental treatments, they turn on myelin production and actually can recoat the nerves.”
Oligodendrocytes wrap around nerve cells and create myelin, Dr. Singer said, noting that in people with MS, 5 percent to 8 percent of the brain and spinal cord cells are immature oligodendrocytes, lying dormant. The goal is to turn on these cells, allowing them to mature so they can be recruited into the MS plaques.
Future remyelination treatments aim to activate these oligodendrocytes, thereby preventing further bodily degeneration and progression of MS, and — perhaps someday — restoring or improving function in those living with MS.
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