Race to Erase MS is a foundation focused on funding new treatments and ultimately a cure for MS, and it supports work at some of the top MS centers in the United States — with the aim of bringing researchers from different institutions together as part of the organization’s Center Without Walls program. The forum took place on May 21, 2022, a day after the 29th annual Race to Erase MS gala, a major fundraiser for the Center Without Walls. Here are some of the top takeaways from the latest forum, in areas including MS drug treatment strategies, better use of imaging to inform MS treatment, and whether mind-altering drugs could have a role to play in treating MS.
Response to COVID-19 Vaccines in People With MS
Erin Longbrake, MD, PhD, a neurologist at Yale University in New Haven, Connecticut, discussed research findings about how well people with MS respond to COVID-19 vaccinations. “There are some differences in terms of how well an MS patient may respond to the vaccination depending on what kind of medication they are taking for their multiple sclerosis,” Dr. Longbrake said. “The good news is that individuals taking most MS medicines have a great response to vaccination.” But people with MS who take a small number of medications — including B-cell-depleting medications such as ocrelizumab (Ocrevus) and rituximab (Rituxan), and sphingosine 1-phosphate (S1P) medications such as fingolimod (Gilenya), ozanimod (Zeposia), ponesimod (Ponvory), and siponimod (Mayzent) — may experience a less robust immune response after receiving a COVID-19 vaccine. People with MS who take one of these medications should consider taking Evusheld for preexposure prevention. Evusheld is a combination of two long-acting antibodies against the virus that causes COVID-19 that is given by injection. It was developed specifically for people with health conditions that may limit their immune response to vaccination, and is approved under an emergency use authorization (EUA) in the United States. While people with MS aren’t necessarily at higher risk for poor outcomes related to COVID-19, some people with MS tend to have worse outcomes if they develop the viral infection — including older people with MS, those with obesity or diabetes, and those with higher disability scores, said Vijayshree Yadav, MD, a neurologist at Oregon Health and Science University (OHSU) in Portland. “Everyone with MS should absolutely get vaccinated against COVID-19,” Longbrake emphasized. “These vaccines are safe and they work.”
Relapses Versus Pseudorelapses in MS
Lilyana Amezcua, MD, a neurologist at the University of Southern California (USC) in Los Angeles, discussed the difference between actual MS relapses and what are known as pseudorelapses — the temporary worsening of neurological symptoms without clinical progression of MS. “When we say ‘relapse,’ we’re really talking about new symptoms or worsening symptoms that are lasting longer than 24 hours,” Dr. Amezcua explained. “In many cases, they start over days and continue on for several weeks.” Importantly, she said, this worsening in an actual relapse is not related to known external factors like infection, temperature changes, or psychological stress. With pseudorelapses, on the other hand, “We’re talking about symptoms that are looking like a new relapse, but they’re not,” said Amezcua. The most common type of infection that may worsen MS symptoms is a urinary tract infection (UTI), and when a UTI is treated, new MS symptoms are often resolved. Other potential causes of pseudorelapses include hot weather, COVID-19 infection, or even COVID-19 vaccination, which can worsen symptoms for about 48 hours in some people. If you experience new or worsening symptoms related to your MS, it’s important to talk to your doctor to help determine whether they might be caused by something like an infection, or whether you’re actually experiencing new disease progression as shown by MRI, said Amezcua. An actual relapse may mean that your MS treatment needs to be intensified or otherwise reevaluated.
Ongoing Research Looks at How Aggressively to Treat Early MS
Ellen Mowry, MD, a neurologist at Johns Hopkins University in Baltimore, discussed how the development of numerous disease-modifying therapies (DMTs) for relapsing-remitting MS has changed the landscape of treatment — and raised the question of how aggressively doctors should treat the early stages of MS. “When someone is newly diagnosed, it can be really tricky to figure out which medication might be right” for a given person, said Dr. Mowry. Based on results from clinical trials, “Some of [the drugs] appear stronger than others in terms of what they’re impacting, which is the occurrence of relapses as well as developing new lesions,” as seen in brain MRIs. But, in fact, many clinical trials show that participants who take milder medications — as well as those who undergo more aggressive treatments — show no evidence of disease progression in the trial. Whether to go with a more aggressive treatment is a dilemma, Mowry noted, because some of the stronger medications have a bigger impact on immune system function — potentially leaving people who take them more vulnerable to infections and other health problems. This potential trade-off has led to a growing interest in studying treatment strategies for using DMTs in MS, rather than simply studying individual drugs. “If you use one of these stronger medications out of the gate, is it going to impact long-term disability more than starting with a more moderate medication?” is a key question for researchers, said Mowry. Right now, she noted, there are two large ongoing clinical trials — led by researchers at the Cleveland Clinic and Johns Hopkins, but taking place at sites across the United States — that are closely examining evidence of disease progression in people taking various DMTs for MS. Researchers want to know, in particular, if there should be a one-size-fits-all strategy for selecting DMTs, or whether some people with certain clinical characteristics might benefit more from stronger treatments early in the course of their MS.
Newer Imaging Technologies Advance the Understanding of MS Progression
Rohit Bakshi, MD, a neurologist and radiologist at Harvard Medical School in Boston, discussed the changing role of imaging in understanding disease processes in MS, and how looking at new brain markers through imaging could inform MS treatment strategies. “There is no doubt that measuring lesions in the white matter, as we do day-to-day, is not sufficient to understand what’s happening to our patients,” said Dr. Bakshi. One other underlying problem is brain atrophy, or widespread loss of tissue in the brain that mostly occurs in the gray matter — where traditional MS lesions aren’t typically found. “A patient with MS may not be having relapses, may not even be having new symptoms, but there is a slow process that’s continuing in these other areas of the brain — which is largely reflected by brain volume loss,” Bakshi explained. “We can see that by looking at MRIs year by year in our patients.” Another potentially important marker seen in brain imaging is microglial activation — whether immune cells known as microglia are activated, an indication of neuroinflammation that may play a role in MS progression. Microglial activation can be seen through positron emission tomography (PET) imaging, which has undergone advances that let doctors use it “in a very fancy way” compared with just a few years ago, according to Bakshi. Certain newer MS therapies are believed to target microglial cells, said Bakshi, and wider use of newer PET imaging techniques may help doctors evaluate how well these treatments are working on the level of brain cell activity, which wasn’t previously possible.
Can Mind-Altering Drugs Help Treat MS?
Adam Kaplin, MD, PhD, a neuropsychiatrist and researcher at MyMD Pharmaceuticals, discussed research on how psychedelic drugs such as ketamine and cannabinoids might play a role in MS treatment. Ketamine is an anesthetic with mind-altering properties when given at lower doses, while cannabinoids are compounds derived from the cannabis plant. Psychedelic drugs have the potential for lasting antidepressant and sometimes anti-addiction effects — even years after people stop using them, Dr. Kaplin explained. “They increase people’s purpose in life and change their personalities to have more openness,” he said. “The critical thing to know is that they change people’s perspective.” The potential for people to be less focused on themselves and more focused on the world and others may be especially helpful for people with MS, Kaplin noted, since it may leave people less focused on their disability or health condition in general. But it’s critical, he noted, that anyone considering using these drugs do so in a structured setting under medical supervision. To reap the benefits that some studies have demonstrated, people need to undergo hours of preparation for the psychedelic experience, followed by the experience itself for several hours, followed by hours of “debriefing” — a long and taxing experience in which many things can go wrong if the right preparations aren’t made. Cannabinoids may be helpful not just for depression, but also for spasticity and neuropathic pain in people with MS, said Kaplin. But more research is needed to look at their long-term track record for mental health, as well as potential cognitive risks such as affecting memory and processing speed in people with MS.
