July 10, 2024 – Almost 1 million Americans are battling the crippling effects of multiple sclerosis (MS) – a relentless disease that could cause damage to the brain, spinal cord and optic nerves.
Worldwide, this number rises to around 2.3 million. While nearly all of patients experience the unpredictable cycles of relapsing-remitting MS (RRMS), which account for 85% of cases, others face the cruel reality of progressive MS, where symptoms steadily worsen and not using a break.
In recent years, the treatment spectrum for RRMS has expanded significantly, offering recent hope and options. Yet effective therapies for individuals with progressive MS remain frustratingly elusive. But there are glimmers of hope on several research fronts that promise possible breakthroughs within the near future. Read on to learn more.
Effects of Multiple Sclerosis
In an individual with MS, the immune system attacks the fatty tissue coverings that protect the nerve cells, called Myelin sheathsThis can result in communication problems between the brain and the remainder of the body.
Because the brain is unable to send the proper signals to the body and the nerves usually are not functioning as normal, individuals with multiple sclerosis may experience a spread of symptoms, including fatigue, blurred or double vision, muscle weakness, difficulty walking, numbness or tingling, and more.
What treatment options are currently available for progressive MS?
The FDA approved an intravenous infusion of a monoclonal antibody called ocrelizumab in 2017 as a treatment for individuals with each relapsing and first progressive MS (PPMS). It works by attacking, binding to and killing B cells and stopping them from entering the brain and spinal cord – where they might normally make myelin. The treatment lowers inflammation levels in MS patients.
Research has shown that giving ocrelizumab infusions every 6 months can reduce the relapse rate and slow the progression of disability in patients with PPMS and RRMS. The results of ocrelizumab were also higher than those of interferon β-1a, a self-administered injection that has been a staple of MS treatment because the Nineties.
Ocrelizumab, sold under the brand name Ocrevus, is the primary – and only – drug of its kind to treat primary progressive MS. It is a component of a broader class of MS drugs generally known as disease-modifying therapies. There are a lot of these drugs available on the market, but most are geared toward treating patients with RRMS. Yet there aren't any therapies to treat the neurodegeneration (lack of nerve cell function) that happens in patients with progressive MS, whose symptoms step by step worsen.
Before the invention of disease-modifying therapies half of patients with RRMS are estimated to develop secondary progressive MS (SPMS) inside 10 to twenty years, and 90% would progress to SPMS inside 25 years.
Unlike the symptomatic ups and downs of RRMS, SPMS progresses slowly and steadily. People with “active” secondary progressive MS still have some periods of relapse, equivalent to recent symptoms or inflammation. In “inactive” MS, patients proceed to experience disease progression without relapse. Although disease-modifying drugs have been very helpful and life-changing in lots of cases, we don't yet know the way well they'll delay the transition from RRMS to SPMS.
“We don't know exactly what causes progressive MS. If you don't know the process you're facing, it's hard to find an effective treatment,” said Dr. Marwa Kaisey, a neurologist who focuses on MS treatments at Cedars-Sinai Medical Center in Los Angeles.
Many of Kaisey's patients fall into the category of inactive SPMS. In these cases, the discussion about treatment options is totally different than for patients with RRMS and PPMS, largely because SPMS acts more like a neurodegenerative disease than an autoimmune disease.
“I'm not saying that progressive and relapsing MS are two different diseases – they're two sides of the same coin,” Kaisey said. “On the one hand, we have great treatment options because it's an autoimmune, inflammatory form of the disease, and on the other hand, we don't because it's less common, gets less attention, and it's just much harder to develop drugs for these types of pathological processes.”
New approaches: BTK inhibitors
Hope for progressive MS treatment will not be lost. Researchers are studying a brand new class of medicine for MS called Bruton tyrosine kinase inhibitors (BTK inhibitors). These drugs are typically used for cancers brought on by abnormal B cells, equivalent to lymphocytic leukemia and lymphoma.
The same kind of defective B cell reproduction can even contribute to the breakdown of myelin, which is why this class of medicine is being investigated as a therapy for MS. There are currently 4 BTK inhibitors in clinical trials, however the FDA has clinical holds in two of those studies resulting from concerns about increased liver enzymes and possible liver damage.
Another blow to the drug's future got here when two studies failed to indicate that BTK inhibitors slowed the annual relapse rate in comparison with other MS drugs available on the market. Despite these challenges, other studies have shown promising results – and researchers usually are not giving up. Many consider that BTK inhibitors are best for Slowing down the progression of MS, making it a potentially significant treatment particularly for progressive MS.
CAR T therapy
Most MS drugs are geared toward treating inflammation, but to this point there isn't a therapy for myelin repair – or remyelination – which might be the important thing to slowing the disease progression. This is where CAR-T therapy is available in.
CAR-T therapy, or chimeric antigen receptor T cell therapy, is one other cancer-fighting immunotherapy being studied for the treatment of MS. During this process, patients' T cells are modified to attack the B cells that attack the body's nervous system in MS patients. Research into CAR-T therapy continues to be in its early stages, but first findings give high hopes.
Use of a dietary complement
Researchers on the University of California, Irvine have found that taking N-acetylglucosamine, a straightforward sugar compound that may be used as a dietary complement, helped reduces inflammation levels in MS patients and has the potential to advertise myelin repair.
Michael Demetriou, MD, PhD, the study's lead writer and an MS specialist at UCI, has had patients taking the complement for over 10 years with little to no negative effects; he's seen how well they do with something so simple as a each day oral complement.
Research will not be yet as advanced as with BTK inhibitors and other available drugs.
“It's a dietary supplement, and the pharmaceutical industry is not interested in developing it because there is no profit motive,” Demetriou said. Since N-acetylglucosamine supplements can be found to anyone who can raise $20, the research is federally funded with help from the National Institutes of Health's Center for Human Immunology, Inflammation and Autoimmunity.
“The difference with the other therapies is that they only have myelin repair activity and cannot treat the chronic active inflammation. I suspect that both are required: You have to treat the chronic active inflammation first and then be able to promote myelin repair,” he said.