Marwa Kaisey, MD
Marwa Kaisey, MD, assistant professor of neurology, Cedars Sinai. She specializes in multiple sclerosis and neuroimmunology.
In January, a scientific study garnered the kind of attention normally reserved for celebrity gossip. Researchers reported that multiple sclerosis (MS), an autoimmune inflammatory disease that causes the body to damage neurons in the brain and spinal cord, is most likely caused by a virus. While this startling news took many people by surprise, MS researchers were not among them.
“We’ve known about this link for decades,” Marwa Kaisey, MD, told Bottom Line Health. What was different was the sheer size of the study (10 million people) and the credibility of the journal it was published in (Science). We asked Dr. Kaisey what these findings mean for people with MS.
The virus in question is called Epstein-Barr virus (EBV), and almost everyone has been exposed to it. It is most well-known for causing mononucleosis, but it can also cause mild cold-like symptoms or no symptoms at all. And it appears that it can cause MS in some people, too.
The team that published the study in Science looked at blood samples from 10 million healthy people on active duty in the U.S. military and found that exposure to EBV—but no other viruses—increased the risk of MS 32-fold. Furthermore, they found an increase in a biomarker of MS-related nerve damage only after EBV infection.
While this convincingly points to EBV as a contributor to MS, it doesn’t mean that it is a singular cause. About 95 percent of people have been exposed to EBV, but only 0.21 percent of Americans have MS. But among the people who do have MS, 100 percent have EBV. It appears that it is impossible to have MS without having had EBV.
This poses exciting questions about prevention. If a vaccine could prevent EBV, could we put an end to all future cases of MS? That’s one of the avenues researchers are already looking at.
Researchers are also exploring a treatment called ATA188. They hypothesize that, in people with MS, the immune system can’t adequately get rid of the virus. Instead, the EBV lingers inside “nests” of B cells. The immune system wants to attack these stowaways, but it can’t differentiate between the virus and healthy cells. As a result, T cells attack healthy cells in the brain and spinal cord instead.
Enter ATA188. In this experimental treatment, T cells are taken from healthy people who have recovered from EBV and engineered so they can cross the blood-brain barrier and destroy the nests of B cells that are harboring the lingering virus.
In a small, yearlong study of people with progressive MS, the treatment looked promising. Out of 24 people, 13 were stable, seven improved, and four got worse.
A year is a short time to look at the effects of the drug, so the people staying stable was to be expected. But seven was an unexpectedly high number of people who got better. Researchers followed the patients who improved and found that the results lasted for at least four years. The team is now enrolling 80 more patients into a phase 2 trial called EMBOLD.
ATA188 is particularly exciting for people with progressive MS, which has few treatment options available. Treatments for relapsing MS, however, are rapidly evolving.
The treatment landscape for relapsing MS has changed dramatically in the last 30 years. Even in the last five years, a lot of new medications have come to market. Getting diagnosed in 2022 is very different than getting diagnosed in 2012.
But that doesn’t mean physicians are keeping up. Doctors who went to medical school a decade ago may not have learned about the latest innovations. In fact, they may still be under the assumption that MS is a difficult disease to treat. That’s simply not true anymore.
Today’s drugs, also called disease-modifying therapies (DMTs), are more powerful than ever. They reduce the number of relapses, delay the progression of disability, and limit new disease activity. Many don’t even have to be taken daily. There are now treatments that you can take every month, every six months, or even yearly. For one called alemtuzumab (Lemtrada), you can take a short course in the first year, a short course in the second year, and then be done indefinitely. While nothing can take away the diagnosis of MS, physicians increasingly have the ability to stop it in its tracks.
DMTs fall into two camps: immune modulators and immunosuppressives. Immune modulators work to rebalance the immune system. (MS is essentially an imbalance that causes the immune system to attack otherwise healthy brain and spinal cord tissue.) Immune suppressants take away a small portion of the immune system. Because different medications take out different portions of the immune system, they have different risks, benefits, and strengths.
During the pandemic, patients and physicians were more likely to avoid drugs that could diminish the immune system and leaned toward immune modulators. But now that we have vaccines and treatments for COVID-19, immune suppressants can safely re-enter the treatment arsenal.
With more powerful medications, there are more risks. But more risk can lead to more reward. In the past, physicians started with the safest and often least powerful drugs and worked their way up the ladder if needed. But now the thinking has shifted to the opposite: If a powerful drug can stop the disease in its tracks and lessen or prevent damage to the brain and spinal cord, it could be worth some added risk. To tease out which of these approaches is best, two clinical trials are comparing them right now: Treat MS (Traditional Versus Early Aggressive Therapy for Multiple Sclerosis) and Deliver MS (Determining the Effectiveness of Early Intensive Versus Escalation Approaches for Relapsing Remitting Multiple Sclerosis).
No treatments can reverse the damage of MS once it’s done, but they could be on the way. Scientists have learned that some people have a limited ability to heal themselves by building back myelin sheaths that protect nerve cells. (MS destroys the myelin sheaths.)
Researchers are investigating how myelin is formed to try to better understand how they can amplify that process and create drugs that will undo the damage.
Stem cell therapy is also being investigated as a one-time treatment. In a small study of 24 people, close to 70 percent remained free of symptoms five years after undergoing treatment. Stem cell therapy is not covered by insurance, as it’s considered to be experimental, but your doctor may know of clinical trials in which you may be able to participate.