July 10, 2024 – Nearly 1 million Americans grapple with the debilitating effects of multiple sclerosis (MS) – a relentless condition that can disrupt the brain, spinal cord, and optic nerves.
Globally, this number swells to around 2.3 million. While the majority of patients endure the unpredictable cycles of relapsing-remitting MS (RRMS), which accounts for 85% of cases, others face the grimmer reality of progressive MS, where symptoms steadily intensify without reprieve.
In recent years, the treatment landscape for RRMS has expanded significantly, offering new hope and options. Yet, for those with progressive MS, effective therapies remain frustratingly elusive. But a glimmer of hope is emerging from various research fronts, promising potential breakthroughs in the near future. Read on to learn more.
Impact of Multiple Sclerosis
When a person has MS, their immune system attacks the sleeves of fatty tissue that protect their nerve cells, called myelin sheaths. This can cause communication issues between the brain and the rest of the body.
With the brain being unable to send the right signals to the body and nerves not working as they normally do, people with multiple sclerosis may have a slew of symptoms, including fatigue, blurred or double vision, muscle weakness, a hard time walking, numbness or tingling, and more.
What Are Current Treatments for Progressive MS?
The FDA approved an intravenous infusion of a monoclonal antibody called ocrelizumab back in 2017 as a treatment for people with both relapsing and primary progressive MS (PPMS). It works by targeting, binding to, and killing B cells, preventing them from entering the brain and spinal cord – where they would normally start myelin. The treatment lowers MS patients’ inflammation levels.
Research has shown that getting ocrelizumab infusions every 6 months can reduce relapse rates and slow the progress of disability for patients with PPMS and RRMS. The results from ocrelizumab have also stacked up better than interferon β-1a, a shot you give yourself that has been a staple in MS treatment since the 1990s.
Ocrelizumab, sold under the brand name Ocrevus, is really the first – and only – of its kind for treating primary progressive MS. It’s part of a wider class of MS drugs known as disease-modifying therapies. There are a lot of these drugs on the market, but most are geared toward treating patients with RRMS. Still, there aren’t therapies out there to address the neurodegeneration (loss of nerve cell function) seen in patients with progressive MS, whose symptoms are gradually worsening.
Before the discovery of disease-modifying therapies, about half of all patients who have RRMS were estimated to develop secondary progressive MS (SPMS) within 10 to 20 years, and 90% would transition to SPMS within 25 years.
Unlike the symptomatic ups and downs of RRMS, SPMS has a slow, steady disease progression. People with “active” secondary progressive MS will still have some periods of relapse, such as getting new symptoms or areas of inflammation. With “inactive,” patients continue to see their disease progress without any relapses. Although disease-modifying drugs have been hugely helpful and life-changing in many cases, we don’t yet know how well they can delay the transition from RRMS to SPMS.
“We don’t exactly know what’s driving progressive MS. When you don’t know the process you’re facing, it’s hard to come up with an effective treatment,” said Marwa Kaisey, MD, a neurologist who specializes in MS treatment at Cedars-Sinai Medical Center in Los Angeles.
A lot of Kaisey’s patients fall into the inactive SPMS category. In those cases, the conversation around treatment options is entirely different than it is for those with RRMS and PPMS, due in large part to the fact that SPMS acts more like a neurodegenerative condition than an autoimmune condition.
“I’m not saying that progressive and relapsing MS are two different diseases – they're very much just two sides of the same coin,” Kaisey said. “But on one side, we have great treatments because it's an autoimmune, inflammatory presentation of the disease, and on the other side, we don't because it's less common, has gotten less attention, and it's just so much more challenging to develop medications for that type of pathologic process.”
New Approaches: BTK Inhibitors
Hope for progressive MS treatment isn’t lost. Researchers have been looking into a new class of drugs for MS called Bruton tyrosine kinase (BTK) inhibitors – drugs typically used for cancers caused by abnormal B cells, such as lymphocytic leukemia and lymphoma.
The same kind of defective B cell reproduction can also contribute to the breakdown of myelin, which is why this drug class is being studied as a therapy for MS. There are four BTK inhibitors in clinical trials right now, but the FDA has placed clinical holds on two of these trials over concerns about higher liver enzymes and potential liver injury.
Another blow to the drug’s future came when two trials failed to show that BTK inhibitors slow down annual relapse rates, compared to other MS drugs on the market. Despite these challenges, other trials have shown promising results – and researchers aren’t backing down. Many believe that BTK inhibitors will be best for slowing the progression of MS, making it a potentially significant treatment for progressive MS in particular.
CAR T Therapy
Most MS drugs are designed to treat inflammation, but so far, there is no therapy out there for myelin repair – or remyelination – which can be the key to slowing disease progression. That’s where CAR T therapy comes in.
CAR T therapy, or chimeric antigen receptor T-cell therapy, is another cancer-fighting immunotherapy being investigated for MS treatment. During this process, T cells taken from patients are modified to target the B cells that, in MS patients, are attacking the body’s nervous system. Research on CAR T therapy is still in its early stages, but initial findings are keeping hopes high.
Using a Dietary Supplement
Researchers from the University of California, Irvine, have found that taking N-acetylglucosamine, a simple sugar compound that can be used as a dietary supplement, has helped ease MS patients’ inflammation levels and has the potential to promote myelin repair.
Michael Demetriou, MD, PhD, the lead author of the study and MS specialist at UCI, has patients who have been taking the supplement for over 10 years with little to no side effects; he’s seen how well they’ve done with something as simple as a daily oral supplement.
The research isn’t as far along as it is for BTK inhibitors and other drugs out there.
“It’s a dietary supplement, so Big Pharma is not interested in developing this because there’s no profit motive,” said Demetriou. Because anyone can get their hands on N-acetylglucosamine supplements if they have $20, the research is being federally funded with the help of the National Institutes of Health’s Center for Human Immunology, Inflammation, and Autoimmunity.
“What’s different about the other therapies is that they only have myelin repair activity, they can't treat the chronic active inflammation – I suspect you need both, that you need to first treat the chronic active inflammation and then be able to promote myelin repair,” he said.
