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Is a Cure for MS on the Horizon?

• New Treatments
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Frequently asked questions.

There is not yet a cure for multiple sclerosis (MS) , and the condition isn't fully understood. But there have been significant advancements in treatment , some of which successfully slow the progression of the disease in many people.

Several new medications have been approved in recent years that slow the course of the disease and reduce symptoms and relapses. Other potential treatments are in trials, including stem cell therapies. And researchers are making progress in understanding the risk factors and causes of MS.

Read on to find out more about the latest research on MS, including the efforts to find a cure for the condition.

sinology / Getty Images

Latest Treatments

Experimental therapies are being explored, as MS treatments and various clinical trials have shown promise. One medication, ibudilast, completed a phase 2 clinical trial in 2018 that showed it can slow the progression of the disease.

Ibudilast is an anti-inflammatory medication that works by reducing inflammation in the body and decreasing the action of a specific enzyme known as phosphodiesterase. Phosphodiesterase breaks down certain organic molecules and, in the process, relaxes muscles and enhances blood flow.

Studies found that while not able to prevent the development of new MS lesions, ibudilast was able to reduce brain atrophy over time compared to a placebo.

The medication can also inhibit certain actions of the immune system that are believed to be behind the nerve cell damage that occurs in the brains of people with MS.

There have also been recent advancements in the use of stem cell therapy for MS. Stem cells are the cells that all other cells in the body are generated from. These cells help the body essentially repair itself.

In 2020, a clinical trial followed patients for one year. In that time:

• About 60% of the patients treated with intrathecal (injected into their spinal fluid) mesenchymal stem cell therapy had no evidence of disease.
• About 40% of the patients treated with intravenous (given in a vein) mesenchymal stem cell therapy had no evidence of disease.
• About 10% of patients in the control group (that did not get a real treatment) had no evidence of disease.

New FDA Approvals

One of the main treatments used to help manage the symptoms and progression of MS is disease-modifying therapies (DMTs). These medications are designed to change the course of MS progression, which ultimately helps reduce its symptoms.

Several new DMT therapies have been approved by the Food and Drug Administration (FDA) to treat and manage MS, including:

• Fingolimod (Gilenya) : First used to treat MS in adults, Gilenya became the first DMT therapy approved by the FDA for use in children with pediatric MS in 2018.  
• Diroximel fumarate (Vumerity) : This medication is similar to an older type of DMT known as Tecfidera. It was approved for use in 2019 after it was shown to possess the same medicinal benefits with fewer side effects.
• Ozanimod (Zeposia) : This medication has been approved to treat three types of MS: clinically isolated syndrome , relapsing-remitting MS , and active secondary progression MS . It received FDA approval in March 2020.
• Ofatumumab, Novartis (Kesimpta) : This injectable medication was approved in 2020 after it demonstrated the ability to reduce MS symptom relapses more effectively than previously used DMTs. It was also shown to reduce disease activity in the brains of people with MS, as seen with scans taken by an MRI machine.
• Ponesimod (Ponvory) : In March 2021, the FDA approved this medication after it was shown to help reduce MS symptom relapses by more than 30%.

Two other oral DMTs were approved in 2019: siponimod (Mayzent) and cladribine (Mavenclad). Both of these treatments were shown to reduce the relapse rate of people with MS.

Cladribine was the first oral medication approved for use as a short-course oral DMT, which means that it is taken for a shorter duration of time. Specifically, people with MS take cladribine in two short-term courses that are one year apart.

Recent Research

Another type of stem cell therapy that is being investigated for MS is called hematopoietic stem cell transplantation (AHSCT). The main goal of this type of therapy is to reset the immune system by using chemotherapy to get rid of harmful immune cells that are causing damage and replace them with healthy immune cells (that were harvested prior to chemotherapy) that can reconstitute the immune system.

This method of treating MS is being explored in clinical trials. According to the National Multiple Sclerosis Society, a call for participants in a new trial was sent out in May 2021.

BEAT-MS Trial

The study is referred to as BEAT-MS, and the participants chosen for the trial will be assigned a specific treatment plan—either AHSCT or another effective treatment called best available therapy (BAT). Once the study begins, each participant will be treated and monitored for six years.

Risk Factors

Research on the risk factors associated with the development of the disease is also underway. While some risk factors are known, others have yet to be discovered.

Some unproven theories that medical researchers have theorized might play a role in the onset of MS include:

• Environmental allergies
• Exposure to house pets
• Heavy metal toxicity
• Exposure to organic chemicals

Viruses and MS

According to the National Multiple Sclerosis Society, researchers are also looking at the possible role of viruses in a person’s risk of developing MS. Several viruses are being investigated, including:

• Epstein-Barr virus
• Human herpes virus 6
• Varicella-zoster virus
• Cytomegalovirus
• John Cunningham virus
• Human endogenous retroviruses

Sex Differences

Research has shown that women are more likely than men to develop MS. However, studies have also found that the type of MS that is more common also varies between the sexes.

While women are more at risk for the disease overall, men are more often diagnosed with a specific type of MS known as primary progressive MS. Men with MS are also more likely to experience a faster disease progression and cognitive impairment than women.  

Finding out why these sex-related disparities exist would help medical researchers develop an optimal treatment for everyone with MS.

Genetic Research

Genetics may play a role in why some people develop MS but others do not. The role of genetic variants in MS is another key research area. A study published in 2018 added four new genes to the more than 200 genetic variants already associated with MS.

Genetic Research and MS

Understanding which genes might increase a person’s risk of developing MS would give medical researchers the information they need to create clinical tools that could help providers treat and possibly prevent MS.

Research has shown that there are several lifestyle factors associated with developing MS. For example, smoking cigarettes, being overweight as a child, and having low levels of vitamin D have all been identified as potential triggers for the disease.

Understanding how other lifestyle influences might affect MS risk could assist researchers in identifying new ways to treat and prevent the disease.

Diet and Gut Health

Diet and chronic disease often go hand in hand. “Gut microbiome” is the term used to describe the collection of living organisms that inhabit the intestines.

The gut microbiome has been a main area of interest for MS researchers. Studies have found that there might be a connection between the state of a person’s gut microbiome and their risk for developing MS.

A study published in 2020 showed that the diversity of the organisms in the guts of people with MS and people without MS were not significantly different. However, there were marked dissimilarities which the researchers said mean that a more long-term and extensive review of MS and the gut microbiome’s possible role in its development is needed.

MS treatments and management techniques have come a long way. The latest advancements in DMTs have given people with MS more options than ever, some providing even fewer side effects than older treatments.

Aside from oral and injectable DMTs—typically the first-line therapies for MS—other experimental treatments such as stem cell therapy have been showing great promise in helping people with MS manage the disease.

The more educated medical researchers become about the potential genetic risk factors and lifestyle choices that may play a role in the development of MS, as well as what causes the disease in the first place, the more equipped they will be to find better treatments.

A Word From Verywell 

As of yet, no cure for MS has been found. However, the major advancements in treatments and the new information that has been learned about the potential causes and risk factors are showing great promise at helping slow or completely halt disease progression in people who do develop MS.

For people with MS experiencing disease progression and worsening of symptoms, the latest FDA-approved treatments might help reduce relapses, which in turn can improve their quality of life.

It’s hard to give an exact timeline for when scientists will find a cure for MS, but new treatments and potential causes (like genetic links) are being explored right now.

Research on MS is exciting and covers a lot of ground. New medications and experimental treatments such as stem cell therapy are being thoroughly investigated. Researchers are also looking at why the disease develops in the first place, which could help them find a way to prevent it.

There is no way to completely halt MS progression, but there are treatments that have been shown to significantly slow it. A type of stem cell therapy known as mesenchymal stem cell therapy is getting close to becoming a treatment that could completely halt MS progression, but more research is needed.

Fox RJ, Coffey CS, Conwit R, et al. Phase 2 trial of ibudilast in progressive multiple sclerosis . N Engl J Med. 2018;379(9):846-855. doi:10.1056/NEJMoa1803583

Petrou P, Kassis I, Levin N, et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis . Brain. 2020;143(12):3574-3588. doi:10.1093/brain/awaa333

Food and Drug Administration. FDA expands approval of Gilenya to treat multiple sclerosis in pediatric patients .

National Multiple Sclerosis Society. FDA approves oral Vumerity™️ (diroximel, fumarate), similar to Tecfidera®, for relapsing MS .

National Multiple Sclerosis Society. UPDATE: FDA-approved oral Zeposia® (ozanimod) for relapsing forms of MS now available for prescription .

National Multiple Sclerosis Society. FDA approves Kesimpta® (ofatumumab), similar to Ocrevus®, for relapsing MS .

Kappos L, Fox RJ, Burcklen M, et al. Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 OPTIMUM study: a randomized clinical trial . JAMA Neurol. 2021;78(5):558-567. doi:10.1001/jamaneurol.2021.0405

Kappos L, Bar-Or A, Cree BAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study . Lancet. 2018;391(10127):1263-1273. doi:10.1016/S0140-6736(18)30475-6

Deeks ED. Cladribine tablets: a review in relapsing MS . CNS Drugs. 2018;32(8):785-796. doi:10.1007/s40263-018-0562-0

National Multiple Sclerosis Society. MS trial alert: investigators recruiting nationwide study comparing AHSCT to other therapies in active relapsing MS .

Immune Tolerance Network. About BEAT-MS .

National Multiple Sclerosis Society. What causes MS?

Tarlinton RE, Martynova E, Rizvanov AA, Khaiboullina S, Verma S. Role of viruses in the pathogenesis of multiple sclerosis . Viruses. 2020;12(6):643. doi:10.3390/v12060643

Eccles A. Delayed diagnosis of multiple sclerosis in males: may account for and dispel common understandings of different MS ‘types’ . Br J Gen Pract. 2019;69(680):148-149. doi:10.3399/bjgp19X701729

Airas L. Hormonal and gender-related immune changes in multiple sclerosis . Acta Neurol Scand. 2015;132(199):62-70. doi:10.1111/ane.12433

International Multiple Sclerosis Genetics Consortium. Low-frequency and rare-coding variation contributes to multiple sclerosis risk . Cell. 2018;175(6):1679-1687.e7. doi:10.1016/j.cell.2018.09.049

Jakimovski D, Guan Y, Ramanathan M, et al. Lifestyle-based modifiable risk factors in multiple sclerosis: review of experimental and clinical findings . Neurodegener Dis Manag. 2019;9(3):149-172. doi:10.2217/nmt-2018-0046

Mirza A, Forbes JD, Zhu F, et al. The multiple sclerosis gut microbiota: a systematic review . Mult Scler Relat Disord. 2020;37:101427. doi:10.1016/j.msard.2019.101427

By Angelica Bottaro Bottaro has a Bachelor of Science in Psychology and an Advanced Diploma in Journalism. She is based in Canada.

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Advances in Multiple Sclerosis Research–Series I

Vasso apostolopoulos.

1 Institute for Health and Sport, Victoria University, Melbourne 8001, Australia; moc.liamg@3591stami

John Matsoukas

2 NewDrug, Patras Science Park, 26500 Patras, Greece

3 Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada

Designing immunotherapeutics, drugs, and anti-inflammatory reagents has been at the forefront of autoimmune research, in particular, multiple sclerosis, for over 20 years. Delivery methods that are used to modulate effective and long-lasting immune responses have been the major focus. This Special Issue, “Advances in Multiple Sclerosis Research—Series I”, focused on delivery methods used for immunotherapeutic approaches, drug design, anti-inflammatories, identification of markers, methods for detection and monitoring MS and treatment modalities. The issue gained much attention with 20 publications, and, as a result, we launched Series II with the deadline for submission being 30 April 2021.

1. Multiple Sclerosis

The World Health Organization estimates that globally, more than 2.5 million people are affected by multiple sclerosis (MS). With the global population growing to an unparalleled height of 7.0 billion in 2011 and recently reaching 7.8 billion (10 October 2020)—it is estimated to reach 8.5 billion by 2030 and 9.7 billion by 2050—the incidence and onset of MS in young adults is expected to rise exponentially, with an estimate of 2.3 million people living with MS globally. Clinical isolated syndrome is a type of MS which may or may not progress. As such, a person will experience a neurological episode lasting at least 24 h and resulting in damage to the central nervous system (CNS). There are three main subtypes of MS, (i) relapse/remitting MS (RRMS) accounting for 85% of MS cases, with 50% progressing to (ii) secondary progressive MS (SPMS), with (iii) 15% of those diagnosed at onset of primary progressive MS (PPMS) type. It is possible that RRMS patients can remain in that state for up to 30 years, whilst 8% develop a more aggressive disease, named highly active RRMS (HARRMS). In rare occasions, up to 5% are progressive relapsing MS type (PRMS), which is characterized by progressive worsening of the condition from the onset, similar to PPMS.

MS is characterized as a chronic demyelinating disorder of the CNS with inflammatory cells infiltrating around the nerve, leading to demyelination of the myelin sheath and immune attack to myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Inflammatory cells which have been found to be involved in MS include macrophages, T helper type 1 (Th1) cells, Th17 cells, CD8+ T cells and B cells secreting auto-antibodies [ 1 , 2 , 3 ]. More recently, it has been shown that tetraspanin-32 is significantly downregulated in Th cells. Tetraspanin-32 controls the development of autoimmune responses, and in EAE models in mice, tetraspanin-32 is significantly expressed at lower levels on activated or encephalitogenic T cells compared to naïve Th cells. In the study by Basile and Cavalli et al., it was noted that tetraspanin-32 was downregulated in memory T cells and was further decreased upon ex vivo restimulation ( Figure 1 ) [ 4 ]. Likewise, myelin-specific memory T cells and peripheral blood mononuclear cells (PBMC) from patients with MS also expressed lower levels of tetraspanin-32 compared to memory T cells from healthy subjects. In addition, MS patients with early relapses compared to those with a longer, stable disease expressed lower levels of tetraspanin-32 on their PBMC [ 4 ]. Hence, tetraspanin-32 is involved in immune responses underlying the pathophysiology of MS, and could be a viable diagnostic marker or therapeutic target against MS.

Summary of new advances in Multiple Sclerosis Research—Series I, papers in the Special Issue. Created with biorender.com.

A number of factors contribute to MS development, including genetic predisposition, especially those who are HLA-DR2 (HLA-DRB1*15, HLA-DRB1*16)- or HLA-DR4 (HLA-DRB1*04)-positive, environmental factors such as Epstein–Barr virus and human herpesvirus 6 exposure, and diet, such as low levels of vitamins B and D [ 1 , 5 , 6 ]. A number of health conditions are related to HLA phenotype, such as type-1 diabetes (HLA-DRB1*03 or HLA-DR3, HLA-DQB1*03 or HLA-DQ8), rheumatoid arthritis (HLA-DRB1*04), juvenile idiopathic arthritis (HLA-DRB1*08), celiac disease (HLA-DQ2, HLA-DQ8) and Graves’ disease (HLA-DRB1*03, HLA-DQA1*0501). The paper by Maria Anagnostouli et al. studied the prevalence of HLA-DPB1 allele in MS patients from a Greek cohort and its association with HLA-DRB1 risk allele [ 7 ]. No significant differences were noted between early onset MS compared to adult onset MS for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles. However, the frequency of HLA-DPB1*03 allele was significantly increased, and the frequency of HLA-DPB1*02 allele was significantly decreased, in AOMS patients compared to controls. Interestingly, the frequency of HLA-DPB1*04 allele was significantly decreased in both patients, with early onset and adult onset MS compared to controls, suggesting a protective role of this allele amongst Greek cohort patients ( Figure 1 ) [ 7 ]. Koukoulitsa and colleagues present a nice review articulating the journey of the conformational complex between HLA-peptide with the T cell receptor of agonist peptides and their altered peptide ligands from MBP, MOG and PLP [ 8 ].

2. Detection and Monitoring of Patients with MS

Magnetic resonance imaging (MRI) has been the gold standard of diagnosing and monitoring disease by detecting brain lesions and the type of brain lesion which aids treatment decisions. In addition, other detection methods are used in combination with MRI, such as the Kurtzke Expanded Disability Status Scale (EDSS) which measures the body’s function and how well it can move, as well as analysis of cerebrospinal fluid for free light chains and IgG. Together, these increase the accuracy of diagnosis of MS and are used to monitor disease progression. However, there are few simple assays available to follow up disease activity. As such, the detection of auto-antibodies from sera is a method to detect relevant biomarkers. The team by Nuti and Papini et al., developed a method to detect anti-N-glycosylated (N-Glc) peptide antibodies, using a four-branched dendrimeric lysine scaffold, linked to a polyethylene glycol-based spacer containing 19-amino acids. This efficient multivalent probe has specificity and high affinity for anti-N-Glc antibodies in patients with MS [ 9 ]. In addition, Gudowska-Sawczuk evaluated cerebrospinal fluid and sera from patients with either MS ( n = 34) or other neurological disorders ( n = 42) [ 10 ]. The concentrations of cerebrospinal fluid κ free light chains (κFLC) and λFLC, and sera κFLC, as well as κFLC, λFLC, and κIgG index, were significantly higher in patients with MS compared to those with other neurological disorders. The κIgG index showed the highest diagnostic power in the detection of MS with both κFLC index and κIgG indexes showing the highest diagnostic sensitivity. This study provides novel information about the diagnostic significance of four markers combined in the κIgG index [ 10 ] and shows that κFLC and κIgG combined in a novel algorithm may improve the detection and disease activity of MS ( Figure 1 ).

Cognitive function refers to a range of high-level brain functions, such as the ability to learn and remember information, solve problems, focus, concentration, attention, and verbal fluency. Change in cognitive function is common in patients with advanced MS. However, Pitteri et al, showed that newly diagnosed RRMS patients ( n = 50) performed worse than healthy controls ( n = 36), in particular, in the domains of memory and executive functioning [ 11 ]. These data demonstrate that reduced cognitive functioning can be present early on during the course of disease, even in patients without evidence of cognitive impairment. As such, the cognitive impairment criteria for patients with MS should be re-evaluated and be monitored closely throughout the course of disease ( Figure 1 ).

3. Treatments for MS

Treatments for MS include, interferon (IFN) beta-1a, IFN beta-1b (cytokines), fingolimod, ozanimod, siponimod (sphingosine-1-phosphate-receptor modulators), natalizumab (a monoclonal antibody against alpha4-integrin), dimethyl fumarate, glatiramer acetate, teriflunomide, cladribine, ocrelizumab (a humanized anti-CD20 monoclonal antibody) and, alemtuzumab (a humanized anti-CD52 monoclonal antibody) [ 1 , 2 ]. These drugs are focused on speeding recovery from relapse, slowing the progression of disease and managing MS symptoms, and in most cases, there are side effects and patients need to stop treatment due to non-tolerance of the treatment. In rare cases, more severe adverse events occur. In fact, Buscarinu et al., presented a case report of a 45 year old Italian woman with RRMS on alemtuzumab treatment who showed immune thrombocytopenic purpura after the second injection of alemtuzumab. Three months following treatment, the patient presented with transient aphasia, cognitive deficits, and focal epilepsy, consistent encephalitis [ 12 ]. Autoimmune complications following alemtuzumab treatment are generally rare, with only one previous case being reported. Furthermore, Sachinvala et al. reported a male patient with MS, and co-morbid type-2 diabetes, major depression, asthma, developed post craniopharyngioma and cranial nerve-VI palsy. Magnetic resonance imaging, Humphrey’s visual filed and retinal nerve fiber thickening were used to determine changes to help the patient maintain productivity and mental state and mood ( Figure 1 ) [ 13 ].

There is a need for the development of new treatment options which would stop progression and have little to no side effects. Immune therapies have come a long way in recent years, with a number of methods being tested in pre-clinical and clinical settings, such as peptide/protein/DNA based vaccines, tolerogenic dendritic cells, T cell receptor peptide immunotherapy, monoclonal antibody therapies (anti-integrin a-4, anti-leucine rich repeat and immunoglobin-like domain-containing protein 1 (LINGO-1), anti-CD52), HLA antagonistic co-polymer therapies, cell specific immunotherapies, peptide-carrier conjugates, all of which are extensively reviewed by Kammona and Kiparissides [ 14 ] and Metaxakis et al. [ 15 ] ( Figure 1 ). An editorial entitled, the long road of immunotherapeutics against MS [ 16 ], highlighted 20 years of MS research of an international multi-disciplinary consortia including peptide chemistry, medicinal chemistry, protein synthesis, protein–peptide interactions, nuclear magnetic imaging, molecular modeling, molecular dynamics, molecular biology, immunology, cell biochemistry, animal research and clinical research. This multi-disciplinary consortia led to at least 10 immunotherapeutic peptide-carrier candidates to be tested in human clinical trials. In preclinical studies, these peptide-based immune modulating conjugates showed a safety profile whilst switching immune responses from pro-inflammatory to anti-inflammatory and protection against experimental autoimmune encephalomyelitis (EAE) in mouse models [ 3 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Characterization of peptide-carrier conjugates was demonstrated using electrochemical voltametric techniques and high-pressure liquid chromatography [ 25 ]. In addition, nanoparticles have been used to deliver MS antigens to the immune system to tolerize T cells or stimulate an anti-inflammatory responses, reviewed by Chountoulesi and Demetzos [ 26 ]. More recently, chloroquine, an anti-malarial drug, was shown to suppress EAE in mice by modulating dendritic cells, Th17 cells, astrocytes, oligodendrocytes and microglia. Microglia cells were also shown to secrete IL-10 and IL-12p70. These data provide evidence that drug repurposing of chloroquine may be useful to patients with MS ( Figure 1 ) [ 27 ].

In the last ten years, the incidence of MS has increased considerably, with lifestyle and environmental factors being one of the main contributors. An informative review by Boziki and Grigoriadis et al., provide the current advances in the gut-microbiome-immune–brain axis in patients with MS with altered microbiome, and present the effects of MS treatments on gut microbiome ( Figure 1 ) [ 28 ]. Thus, modification of gut microbiota by either dietary (such as, probiotics) or medicinal approaches is a promising approach for the management of MS. In fact, probiotics have been shown to have beneficial effects not only in the gut flora but also in modulating and maintaining a healthy immune system. Certain probiotics have been shown to have anti-inflammatory effects on immune cells (i.e., monocytes) and in disease settings, such as asthma and allergies [ 29 , 30 ]. The paper by Dargahi et al. showed that the probiotic Streptococcus thermophilus was able alter pro-inflammatory T cells responses against an agonist MBP 83–99 peptide to an anti-inflammatory profile ( Figure 1 ) [ 31 ]. This study suggests that the consumption of Streptococcus thermophilus may be beneficial in the management and treatment of autoimmune diseases such as MS, and further research in this area is warranted.

In addition to intravenous or oral steroids that are used as the first line of therapy for MS relapse, therapeutic plasma exchange, or plasmapheresis, is another method used to treat patients with neuromyelitis optica spectrum disorders, autoimmune encephalitis and MS, especially those with sudden, severe attacks or relapse/flare-ups. It is used in MS patients to manage disease by exchanging their plasma with ‘fresh’ plasma to remove pro-inflammatory cytokines and other proteins involved in auto-immune attack. In a study published by Moser et al., in this Special Issue, they compare the indications, efficacy and safety of therapeutic plasma exchange treatment in MS, autoimmune encephalitis and other immune-mediated CNS disorders and noted consistent efficacy and safety [ 32 ]. Measuring biomarkers of inflammation and oxidative stress is important to understand the efficacy of treatments. As such, Moccia et al. studied 60 patients with RRMS who were treated with IFN beta-1a or Coenzyme Q10 and monitored patients for IL-1b, IL-2R, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-13, RANTES, tumor necrosis factor and uric acid ( Figure 1 ) [ 33 ]. These serum biomarkers could be used to determine the efficacy of treatments as well as their mechanisms of action.

It is believed that transcranial magnetic stimulation motors with direct current stimulation (tDCS) intensities induce physiological changes to the brain, although the mechanism of action, as well as its validity and efficacy, are not clear. In a pilot study by Workman and colleagues, they noted that there were no immediate changes in cerebral blood flow following direct current stimulation. Hence, further work is required to enable sufficient magnitudes of intracranial electrical fields to induce physiological changes in the brain to patients with MS ( Figure 1 ) [ 34 ]. During disease progression, patients with MS develop walking limitations, and fampridine is usually recommended to improve gait. In the study by Ahdab et al., fampridine was evaluated for cortical excitability effects and whether changes could predict therapeutic responses in 20 patients with MS and gait impairment [ 35 ]. It was noted that fampridine increased the excitatory intracortical processes, as shown by paired-pulse transcranial magnetic stimulation, suggesting that this could be used to select patients with MS who would be likely to experience a favorable response to fampridine ( Figure 1 ) [ 35 ].

4. Conclusions

The development of drugs, immunotherapeutics and vaccines against diseases is a long process often taking researchers a lifetime. In this Special Issue, “Advances in Multiple Sclerosis Research—Series I”, a range of papers were published, including MS markers, treatments, detection, monitoring and the role of the microbiome in MS. Together, all this information advances our knowledge of MS research, with promising new leads being developed in the next few years and entering human clinical trials.

Acknowledgments

V.A. would like to thank the Institute for Health and Sport, Victoria University for supporting her current efforts into MS research. J.M. would like to thank the General Secretariat for Research and Technology (GSRT) and Patras Science Park for supporting his MS research.

Author Contributions

Conceptualization, writing, review, editing: J.M., V.A. Both authors have read and agreed to the published version of the manuscript.

The writing of this editorial received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

What’s New in MS Research – September 2023

Reviewed by MSAA Chief Medical Officer Barry A. Hendin, MD

In this Article

For first time, ms therapies included on who list of essential medicines.

In another first, the FDA approves 
a biosimilar for relapsing forms of MS

Phase I study looks at ANK-700, an experimental “inverse vaccine” for MS

Ibudilast shows favorable effect on measure linked to disability progression in progressive ms, encouraging news on ocrevus ® for people with primary-progressive ms.

Aubagio ® Cuts risk of first demyelinating event in people with radiologically isolated syndrome

Multi-protein blood test offers insights into MS disease activity

Predicting non-relapsing progression following anti-cd20 therapy for ms, study shows no link between vaccination and hospitalization for ms flare-ups, pinpointing a way to relieve fatigue in ms study shows short-term benefits of acupuncture, cannabinoid-based mouth spray relieves ms spasticity in two trials, for more information.

This edition of “What’s New in MS Research” opens with a pair of “firsts:” the first listing of multiple sclerosis (MS) therapies on the World Health Organization’s List of Essential Medicines and the first United States Food and Drug Administration (FDA) approval of a biosimilar therapy for the long-term treatment of MS.

Those developments reflect an increasing awareness among public health officials internationally and in the United States that it is critical for people with MS to have access to the therapies that can make a real difference in their lives.

The other items in this iteration of “What’s New in MS Research” highlight the many avenues of inquiry researchers are pursuing to develop, assess, and optimally employ disease-modifying therapies (DMTs), other MS-focused treatments, and additional interventions to promote the overall health and well-being of people living with multiple sclerosis.

The World Health Organization (WHO) in July 2023 added three disease-modifying therapies (DMTs) for multiple sclerosis to its list of “Essential Medicines,” marking the first time that MS treatments have been included on the roster. 1

The DMTs added to the list are Mavenclad ® (cladribine); glatiramer acetate, which is marketed as Copaxone ® and in a generic formulation; and rituximab, which is marketed in the United States as Rituxan ® . While Rituxan has many FDA-approved uses in cancer and other conditions, it is not approved in the United States for the treatment of MS.

The WHO said that it chose those medications for its list because all three have been shown to delay or prevent progression of MS and because they have different routes of administration, prices, and roles in treating the disease. Mavenclad is provided as tablets taken by mouth, while glatiramer acetate is given by injection, and rituximab is administered by intravenous infusion. In a press release, the organization explained that adding MS therapies to its list “is aimed at facilitating improved access to treatment for people living with MS around the world. The decision to support off-label use of ritixumab is supported by strong evidence of its efficacy and safety for this indication.”

The MS Coalition (MSC), a network of nine member organizations that include MSAA, applauds the WHO’s inclusion of MS disease-modifying treatments (DMTs) on the Essential Medicines List (EML) as part of its commitment to brain health. As the MSC notes, “This decision is an important step to increasing worldwide access to life-changing medications. Affordable access to DMTs is essential for all people with MS and aligns with the Coalition’s mission to improve the quality of life for those affected by MS. While there are far more DMTs available in some parts of the world, the inclusion of these DMTs on the EML list represents a giant step forward towards equitable access around the world.”

In addition, MSAA would like to recognize the MS International Federation (MSIF) for their vital role in advocating for this urgently needed inclusion of MS disease-modifying treatments (DMTs) on the WHO Essential Medicines List. Headquartered in London, the MSIF is a unique global network of 48 MS organizations as well as members of the MS community – including people with MS, volunteers, and staff in many countries. In collaboration with other health groups, the MSIF applied for the inclusion of MS medications in December 2022, following several years of work toward this goal by experts from around the world.

Beyond the specific therapies the WHO chose to place on the list, this first-ever inclusion of DMTs represents an important precedent for MS medications as a whole and recognition of the need to provide people with MS with ready access to therapies.

In another first, the FDA approves a biosimilar for relapsing forms of MS

In August 2023 the Food and Drug Administration (FDA) approved Tyruko ® (natalizumab-sztn), making that medication the first biosimilar to be approved for the long-term treatment of MS. 2

Marketed by Sandoz, Tyruko is a biosimilar to Tysabri ® (natalizumab), a disease-modifying therapy for MS that was approved in 2004 and is given via IV infusion every four weeks. The advantages of having generic, biologic, and biosimilar products available often include greater accessibility to the medication, potential savings, and continued product development through competition.

According to the FDA, “Biological products include medications for treating many serious illnesses and chronic health conditions, including MS. A biosimilar is a biological product that is highly similar to, and has no clinically meaningful differences from, a biological product already approved by the FDA (also called the reference product). This means patients can expect the same safety and effectiveness from the biosimilar as they would the reference product.”

As with Tysabri, Tyruko is approved to treat relapsing forms of MS, which include clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS). Because it is a biosimilar, Tyruko is given at the same dosage and via the same administration as Tysabri, while also carrying the same benefits and risks.

Tysabri’s benefits – when compared to placebo over a two-year period – include a 67% decrease in the number of relapses, a 92% reduction in lesions, and a reduction in disability progression (42% reduction over three months and 54% reduction over six months). Common side effects include headache and fatigue, infections such as upper respiratory tract infection (URTI) and urinary tract infection (UTI), as well as infusion reactions.

Tysabri is a monoclonal antibody that acts against a molecule involved in the activation and function of lymphocytes, which are immune system cells produced to fight infection and disease. It also acts against the passage of lymphocytes into the central nervous system (CNS). Tysabri increases the risk of progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal brain infection caused by the JC virus. Given that natalizumab products increase the risk of PML, all such medications are required to have dedicated Risk Evaluation and Mitigation Strategy (REMS) programs.

With MS, the immune system becomes misdirected and attacks the myelin and the nerves of the central nervous system (CNS). Following successful results in a study of mouse models with experimental autoimmune encephalitis (EAE), an induced illness that causes MS-like symptoms and damage, ANK-700 is currently being tested in humans for safety. This experimental treatment is often referred to as an “inverse vaccine,” which means that rather than train the immune system to attack specific targets such as those that cause infection, ANK-700 is designed to train the immune system to be tolerant of specific targets: in this case, the body’s own myelin.

With regard to the mouse models, researchers found that both for those with a relapsing form of EAE or a progressive form, a research candidate with the same type of “inverse vaccine” design was able to stop the immune system’s attack on myelin. The nerves of the treated mice were able to regain function and the MS-like symptoms were reversed.

According to an article published online by Multiple Sclerosis News Today, “Scientists previously discovered immune tolerance against a target could be achieved by tagging the target with a sugar molecule called N-acetylgalactosamine or pGal. This molecule prompts the target to be taken up by regulatory immune cells that activate tolerance processes in other immune cells.” 3

A press release from the University of Chicago’s Pritzker School of Molecular Engineering (PME) explains that this new type of vaccine developed by their researchers “has shown in the lab setting that it can completely reverse autoimmune diseases like multiple sclerosis and type 1 diabetes — all without shutting down the rest of the immune system.” 4

Readers should note that initially, many experimental treatments for MS show positive results in animal studies, but only a small fraction of these treatments advance to human studies and ultimately show both safety and efficacy. While ANK-700 still has a long road of studies ahead to see how it may affect disease activity in individuals with MS, these types of experimental treatments are exciting to hear about and provide much hope for the future. This study was funded by ANK-700’s developer, Anokion, and details were published on September 7, 2023 in Nature Biomedical Engineering. 5

The anti-inflammatory medication ibudilast preserved the integrity of brain tissue in people with progressive forms of MS in a Phase II clinical trial, researchers reported. 6

Ibudilast is an oral medication used to treat asthma in Japan and South Korea. The biopharmaceutical company MediciNova is evaluating the therapy for potential roles in progressive forms of MS, amyotrophic lateral sclerosis (ALS), and other conditions.

Researchers analyzed data from the SPRINT-MS trial to evaluate the impact of ibudilast on tissue integrity and volume in the thalamus, a small, grey matter structure of the brain that relays motor and sensory signals to other regions of the brain.

In the trial, 255 people with progressive MS were assigned in a random fashion to receive either ibudilast or placebo. Investigators then used magnetic resonance imaging (MRI) to assess the thalamic magnetization transfer ratio (MTR), which is a measure of tissue integrity and demyelination, and thalamic volume (TV) over 96 weeks.

Relative to placebo, ibudilast had a more favorable impact on thalamic MTR. Noting that thalamic MTR is associated with confirmed disability progression, the researchers said that this finding suggested “a clinically relevant effect on thalamic tissue integrity.” However, ibudilast was not shown to have an effect on thalamic volume, which the investigators said suggested “that thalamic atrophy is more closely associated with global inflammatory activity than local tissue integrity.”

The findings follow publication of the SPRINT-MS trial’s main results in The New England Journal of Medicine in 2018. 7 The study found that, relative to placebo, ibudilast cut the rate of brain atrophy – the trial’s primary endpoint – roughly in half over 96 weeks. This latest analysis builds on that welcome news and provides further hope that the years ahead will see an expansion of the treatment choices available for people with primary-progressive and secondary-progressive MS.

In 2017, Ocrevus ® (ocrelizumab) became the first disease-modifying therapy approved by the Food and Drug Administration (FDA) for the treatment of primary-progressive multiple sclerosis (PPMS). The FDA’s approval was based on the results of the Phase III ORATORIO trial, which found that people with PPMS who received Ocrevus had lower rates of disease progression than study participants who received placebo. 8

The approval represented a great advance for people with PPMS (while several investigational medications currently are being evaluated in PPMS, Ocrevus remains the only FDA-approved therapy for the condition). However, ORATORIO limited its assessment of Ocrevus in people with PPMS to those who were 18 to 55 years of age, who had an Expanded Disability Status Scale (EDSS) score of 3.0 to 6.5, and who met other requirements. Because of those criteria, patients and clinicians have not had data on the efficacy and safety of the medication in people older or younger than the study population or in those with an EDSS score lower or higher than the range included in the trial. (The EDSS runs from 0 to 10, with a higher score indicating greater disability.)

A group of Italian researchers recently helped fill in that evidence gap by conducting a retrospective study that compared outcomes in people with PPMS who did, and did not, meet the age and EDSS criteria used in ORATORIO. 9 The study focused on 589 people who were treated with Ocrevus between May 2017 and June 2022. Of the total, 149 met the ORATORIO criteria and 440 did not.

The researchers found that people in both groups had a similar probability of experiencing clinical progression over time. For example, the cumulative probability of clinical worsening by two points or more on the EDSS scale over 12 months was 3.4% in both groups. Over 24 months, that probability was 5.4% in the ORATORIO group and 5.0% in the non-ORATORIO group. Interestingly, no significant differences in 12-month and 24-month clinically worsening were noted based on baseline EDSS score. People aged 56 to 65 years fared similarly to those aged 18 to 55 in terms of clinical status, but those aged 66 years and older were more likely than the ORATORIO group to experience clinical worsening over one or two years. Of course, this finding could reflect the interplay between the MS disease process and aging. Meanwhile, having had PPMS for more than 10 to 15 years did not appear to limit the impact of Ocrevus.

One of the key strategies in the fight against MS has been to determine the effectiveness and safety profile of a medication in a specific group of people and then explore whether that therapy also has a role in treating a broader population. This study by Italian researchers is both a classic example of that strategy succeeding and heartening news to many people living with PPMS.

The researchers studied 35 patients to explore how unmet needs, quality of life, and depression in older people with MS and in people with advanced MS differed from those of younger people with MS who were fully independent. Twenty-one people participating in the study were aged 64 or younger and did not require assistance with daily activities. These people served as the control group against which older people and those with an Expanded Disability Status Scale score of 7 or higher, indicating advanced MS, were compared.

While researchers noted that the better mental QoL among older people with MS relative to younger people was surprising, they did not offer potential explanations for the finding. They did say, however, that they plan to conduct future studies to look deeper into these results and to better understand the needs of older people with MS and people with advanced MS.

Aubagio ® cuts risk of first demyelinating event in people with radiologically isolated syndrome

People with radiologically isolated syndrome (RIS) who took the disease-modifying therapy Aubagio ® (teriflunomide) saw their risk for a first clinical demyelinating event reduced by 72% relative to people with RIS who received placebo in a 96-week study. 10

The phase III randomized clinical trial was conducted from September 2017 to October 2019 at MS referral centers in France, Switzerland, and Turkey. The study involved 89 people, all of whom met the criteria for RIS, which the study’s authors noted is the earliest detectable preclinical phase of MS.

A person is classified as having RIS when magnetic resonance imaging (MRI) scans find white matter abnormalities consistent with MS in the brain or spinal cord even though the person has no clinical signs or symptoms of the disease. RIS often is identified when a person has an MRI for another reason, such as to evaluate the brain after a car accident or fall. Epidemiological studies indicate that as many as half of people with RIS will go on to be diagnosed with clinically definite MS over the following 10 years.

The study’s participants had an average age of 37.8 years. Seventy-one percent were female. Forty-five of the participants received 14 mg daily of Aubagio while the other 44 participants received a placebo. Nine people in each group stopped participating in the study for reasons that included adverse events, withdrawal of consent, lack of follow-up information, and pregnancy.

Researchers found that the unadjusted risk for a first clinical event in people receiving Aubagio was 63% lower than the risk for people in the placebo group. After adjusting for differences in the two groups in accord with standard statistical protocols, the people receiving Aubagio had a 72% lower risk relative to the placebo group.

The safety profile of Aubagio in the study was consistent with that seen in earlier studies of the oral DMT, which is approved by the FDA for treatment of relapsing forms of MS.

Learning that an MRI scan obtained for an unrelated reason shows evidence of a potential precursor to MS is disturbing enough, but the anxiety can be compounded by the fact that there currently is no FDA-approved therapy for RIS. This study, and others evaluating different DMTs for their potential use in RIS, provides hope that people diagnosed with the syndrome may have effective, evidence-based treatment options in the future.

Clinicians may one day be able to use a multi-protein blood test to assess disease activity in a person with MS, including determining the likelihood of active inflammation in central nervous system lesions.

A team of researchers recently reported on their assessment of the MS Disease Activity (MSDA) test, which analyzes 18 proteins found in the blood. 11 The researchers drew on blood samples, imaging results, and clinical data from 426 people with MS to develop an algorithm and establish performance specifications for the test.

The researchers then evaluated the test and its algorithm in a separate group of 188 people with MS. As part of that process, they compared the MSDA with the single-protein biomarker that they found to have the highest performance for different disease activity endpoints. Blood levels of that protein, neurofilament light chain (NfL), have been shown in a number of studies to help predict disease course in MS. (See related item below, “Predicting non-relapsing progression following anti-CD20 therapy for MS.”)

In “testing the test,” the investigators found that MSDA scores aligned well with overall disease activity and the presence of gadolinium-enhancing lesions on magnetic resonance imaging. (Gadolinium enhancement typically signifies inflammatory activity within an MS lesion.) For example, the odds of having one or more gadolinium-enhancing with a moderate/high disease activity (DA) score were 4.49 times those of a low DA score, the investigators reported. Further, the odds of having two or more such lesions with a high DA score were 21 times those of a low/moderate score. The researchers noted that the MSDA outperformed NfL in terms of identifying active versus stable MS as defined by a mix of imaging and clinical evidence.

The investigators wrote, “With the successful clinical validation of the MSDA Test, we envision several potential uses in the future, including a routine surveillance test to better monitor disease activity and progression (e.g., distinguish inflammation from silent disease progression), especially in patients considered to have stable disease, and to track new/worsening symptoms, as well as an evaluation test of treatment response, or in consideration of alternative treatment options.”

The MSDA is not yet available for use in clinical practice. The researchers noted that it would be valuable to further evaluate the test in a larger population and in a real-world setting. There also will be regulatory requirements to address, and payers must agree to provide reimbursement for the test. Nonetheless, the ability to draw on multiple proteins in the blood to assess various aspects of MS disease activity represents a major advance in the effort to evaluate and manage multiple sclerosis in a comprehensive manner.

No news is not always good news when it comes to MS. That’s because disease progression can occur even in the absence of an obvious relapse or less-dramatic evidence of clinical worsening, making it difficult for clinicians and patients to know if a therapy is working or if a new approach may be warranted.

Now, however, researchers analyzing data from studies that led to the FDA’s approval of Ocrevus ® (ocrelizumab) for relapsing and progressive forms of MS have found that blood levels of neurofilament light chain (NfL) can help predict non-relapsing progression following treatment with that therapy, which targets the CD20 protein on the surface of B cells. 12

NfL is a protein found in axons, the segment of a neuron that carries electrical impulses away from the main portion of the nerve cell, facilitating transmission of those impulses from one neuron to another. When axons coated with myelin are injured, they release NfL into the cerebrospinal fluid. From there, the protein enters the blood stream. Most research on NfL has examined its role as a marker of acute events, such as relapses. In this study, however, investigators wanted to see whether NfL levels also could provide insights into more-subtle changes in MS course. They explained, “We used ocrelizumab’s ability to robustly suppress acute disease activity as an opportunity to assess the utility of NfL for monitoring risk for relapse-independent clinical progression following treatment initiation.”

The researchers analyzed baseline and subsequent blood levels of NfL in 1,421 people with relapsing MS and in 596 people with primary-progressive MS, evaluating more than 11,800 blood samples and following patients for as long as nine years.

And what did they find? Researchers found that long-term disability progression can still occur in the absence of observable disease activity, i.e., a relapse or clinical worsening, and elevated blood levels of NfL may predict the risk of such progression. In this study, after administration of Ocrevus, which suppressed relapse activity, patients who had persistently elevated levels of serum NfL at Week 24 and Week 48 were at increased risk of long-term disability progression. Researchers said this heightened risk was seen in both people with relapsing MS and those with primary-progressive MS.

The investigators concluded, “Suppression of relapsing biology with high-efficacy immunotherapy provides a window into the relationship between NfL levels and future non-relapsing progression.” This window can offer an important perspective not only on the management of individual patients but also into strategies for drug development.

People with MS who received one of several different types of vaccines were no more likely to be hospitalized for an MS flare-up in the 60 days after they were vaccinated than they were in the 60 days – or longer – before vaccination.

That was the main finding of a French study that examined records on more than 100,000 people with MS to investigate the common – but not scientifically supported – concern that vaccination may trigger MS flare-ups. 13

Researchers analyzed an average of 8.8 years’ worth of data on the study subjects, 71.8% of whom were female. The people included in the analysis had an average age of 43.9 years. Roughly two-thirds had been diagnosed with MS for at least two years. Seventy percent had used at least one disease-modifying therapy.

Vaccines analyzed in the study included those for influenza, pneumococcal diseases, and diphtheria, tetanus, poliomyelitis, pertussis, and Haemophilus influenzae (the DTPPHi vaccine). All of the vaccines were inactivated, meaning that they did not contain live viral or bacterial material. Vaccines against COVID-19 were not included in the analysis because the period studied ran from January 2007 to December 2017, ending roughly two years before the coronavirus outbreak.

Of the 106,523 people studied, 35,265 – or one-third – were hospitalized for an MS flare-up on at least one occasion over the average 8+ years for which data was available on them. The adjusted odds ratio (aOR) of being hospitalized for an MS flare-up in the 60 days after receiving any one of the vaccines studied was 1.00. This means that a person was no more and no less likely to be hospitalized for an MS flare-up in the 60 days after vaccination than in the comparable period prior to vaccination. (By comparison, an aOR of 1.5 would represent a 50% increase in likelihood of hospitalization and a 2.0 aOR would represent a doubling of risk.)

Turning to specific vaccines, the aOR was 0.95 for the DTPPHi vaccine, 0.98 for the influenza vaccine, and 1.20 for the pneumococcal vaccine, which acts against the bacterium Streptococcus pneumoniae, and which can help prevent some cases of pneumonia, meningitis, and sepsis.

The investigators explained that, to their knowledge, their study is the most extensive research conducted to date on the risk of being hospitalized for an MS flare-up following vaccination. They added that examining this topic is essential because infections are known to increase the risk of MS flare-ups and to exacerbate symptoms, making it imperative that people with MS take steps – such as vaccination – to avoid infection. Further, they noted that “a possible association between vaccination and the onset of MS is the source of a decade-long debate,” adding that the inconclusive evidence and ongoing debate over that separate question “has spurred doubts and potentially detrimental vaccination hesitancy” among people who already have MS.

The researchers added that the strengths of their study included the large number of people in the analysis and the long follow-up period. Despite its size, however, the researchers noted that, “The study cannot completely rule out the existence of a small risk, particularly in the case of the pneumococcal vaccine.” They added, “considering the number of vaccine subtypes available, further studies are needed to confirm these observed results.”

While offering those important caveats, the researchers summed up their findings by noting, “We did not observe an association between the risk of hospitalization for an MS flare-up and vaccination, considered overall or individually, regardless of the age group studied.”

Guidelines from medical societies and multiple sclerosis advocacy organizations identify administration of inactivated vaccines as a key means of protecting the health of people with MS. The guidelines note that an individual should not receive a specific vaccine if he or she has a contraindication to it, and caution against giving vaccines while a person is experiencing an active flare-up of their MS.

With “flu” season fast approaching and an uptick in COVID-19 cases, it is important for people with MS to talk with their clinicians about which vaccines may be appropriate for them and about the risks and benefits associated with each vaccine. This large study hopefully will help to inform that discussion and provide some reassurance in terms of vaccination risk, which, of course, must be balanced against the risk that comes from not being vaccinated.

Four weeks of acupuncture significantly relieved fatigue in an international study of 60 people with relapsing-remitting MS. 14

All of the study participants reported fatigue, were not experiencing an MS exacerbation during the trial, and were given the medication amantadine. (In the United States, amantadine is approved by the FDA to prevent and treat influenza, to treat Parkinson’s disease and related conditions, and to treat movement problems that occur as side effects of certain medications. In other countries it also is used to treat MS-related fatigue, and some clinicians in the U.S. prescribe it “off-label” for that purpose.)

The study subjects were randomized into two groups of 30 people each. People in the first group received acupuncture treatment two to three times a week for a total of 10 sessions over four weeks. They also received 100 mg of amantadine daily, as well as whichever disease-modifying therapy (DMT) they were taking, if any. People in the other group took daily amantadine plus any DMT that had been prescribed for them. The study’s primary endpoint was change from baseline in the Fatigue Severity Score (FSS). The secondary endpoint was change from baseline in the Multiple Sclerosis Quality of Life 54 (MSQOL-54) questionnaire score.

Both groups saw their fatigue reduced over the course of the four-week study, but people in the acupuncture group had a greater reduction in fatigue than their counterparts in the control group. They also had greater improvement in their quality of life, including in both physical and mental status, than those in the control group. All of those differences were statistically significant. No adverse events were reported in either group.

In keeping with the adage that “everything old is new again,” the ancient practice of acupuncture – administered by properly trained and licensed personnel – may offer new hope to the estimated two-thirds of people with MS who experience fatigue.

People experiencing MS-related spasticity who made daily use of an oral spray containing cannabinoids experienced significant improvement in several measures of spasticity over 12 weeks, according to researchers. 15

Those investigators analyzed results of two trials of nabiximols, a spray developed as a treatment for MS spasticity that is approved for use in European Union countries and elsewhere in the world, but which is not approved by the Food and Drug Administration for use in the United States. Nabiximols is a botanical mixture that contains delta-9-tetrahydrocannibinol (THC) and cannabidiol (CBD) from cannabis plants, as well as other non-cannabinoid ingredients.

Measures examined included patients’ daily self-reported scores from 0 to 10 on the Spasticity Numeric Rating Scale (NRS), patients’ daily spasm counts, and clinicians’ assessment of their patients’ spasticity using the modified Ashworth scale (MAS).

Both studies had an initial stage, Part A, in which all patients received nabiximols. Those who had a 20% or greater improvement in their Spasticity NRS score in Part A went on to the second stage, Part B, in which half of the people received nabiximols and half did not. Researchers use this two-step approach so they can first identify people who respond to a medication and then go on to study the impact of the medication relative to placebo only in a population of known responders. This can yield more valuable information on a medication than studying the therapy in a larger population in which the percentages of responders and non-responders are unknown at the outset.

In the first study, 124 people were randomly selected to use nabiximols, plus whatever other spasticity medicines or therapies they were receiving, while 117 people were randomized to receive placebo plus their current treatments, if any. The second study was limited to people who had not obtained adequate relief from two prior anti-spasticity medications and who were on current treatment for the condition. In that study, 53 people were randomized to receive nabiximols and 53 were assigned to the placebo group.

In Part B of both studies, participants receiving nabiximols had more favorable changes from baseline in their daily Spasticity NRS scores than their counterparts in the placebo group. Further, patients receiving nabiximols in the first study had a 19% greater reduction in daily spasms than people on placebo, while that difference stood at 35% in the second study. People receiving nabiximols also had better results in terms of change in spasticity as measured by the modified Ashworth scale, with the greatest benefits seen in the leg muscles.

The researchers reported that nabiximols were generally well tolerated by people in both studies. Urinary tract infections were the most frequently reported adverse events, affecting 7% of people receiving nabiximols in the first study. Other issues reported included vertigo, fatigue, nausea, dry mouth, dizziness, and sleepiness, with each condition affecting less than 10% of people receiving nabiximols There were six serious adverse events in the nabiximols group in the first study, while one person in that study’s placebo arm had a serious adverse event. In the second study, one patient in each group had a serious adverse event. In the first study, 7% of people in the nabiximols group stopped participating in the trial due to adverse events; none of the patients in the second study withdrew from the trial because of side effects.

Research has shown that a majority of people with MS are affected by spasticity. Many of those people report receiving insufficient relief from currently available therapies. This analysis of two studies suggests that another approach, not currently available, may someday help address a significant unmet need for people in America living with MS-related muscle spasms and stiffness.

• World Health Organization. WHO endorses landmark public health decisions on essential medicines for multiple sclerosis. July 26, 2023. Available at https://www.who.int/news/item/26-07-2023-who-endorses-landmark-public-health-decisions-on-essential-medicines-for-multiple-sclerosis . Accessed September 15, 2023.
• U.S. Food and Drug Administration (FDA). FDA approves first biosimilar to treat multiple sclerosis. August 24, 2023. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-treat-multiple-sclerosis . Accessed September 15, 2023.
• Tremain, A.C., Wallace, R.P., Lorentz, K.M.  et al.  Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses.  Nat. Biomed. Eng   7 , 1142–1155 (2023). [found at  Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses | Nature Biomedical Engineering ]
• Wexler, M. ‘Inverse vaccine’ approach lowers disease in MS mouse model: ANK-700 is being tested in early MS clinical trials.  Multiple Sclerosis News Today . September 14, 2023. Accessed online September 22, 2023 at  MS disease activity in mice lowered with ‘inverse vaccine’ technique | Multiple Sclerosis News Today
• Williams, SCP. “Inverse vaccine” shows potential to treat multiple sclerosis and other autoimmune diseases.  University of Chicago’s Pritzker School of Molecular Engineering (PME) News . September 11, 2023. Accessed online September 22, 2023 at   “Inverse vaccine” shows potential to treat multiple sclerosis and other autoimmune diseases | Pritzker School of Molecular Engineering | The University of Chicago (uchicago.edu)
• Nakamura K, Zheng Y, Ontandea D, et al. Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis. Mult Scler J . 2023;29(10). doi.org/10.1177/13524585231187289.
• Fox RJ, Coffey CS, Conwit R, et al. Phase 2 trial of ibudilast in progressive multiple sclerosis. N Engl J Med . 2018;379:846-55.
• Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med . 2017; 376:209-220.
• Chisari CG, Bianco A, Brescia Morra V, et al. Effectiveness of ocrelizumab in primary progressive multiple sclerosis: a multicenter, retrospective, realworld study (OPPORTUNITY). Neurotherapeutics . 2023. doi.org/10.1007/s13311-023-01415-y.
• Lebrun-Frenay C, Siva A, Sormani MP, et al. Teriflunomide and time to clinical multiple sclerosis in radiologically isolated syndrome: the TERIS randomized clinical trial. JAMA Neurol . Published online August 21, 2023. doi:10.1001/jamaneurol.2023.2815.
• Chitnis T, Foley J, Ionete C, et al. Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis. Clin Immunol . 2023;253.109688.
• Bar-Or A, Thanei G-A, Harp C. Blood neurofilament light levels predict non-relapsing progression following anti-CD20 therapy in relapsing and primary progressive multiple sclerosis: findings from the ocrelizumab randomised, double-blind phase 3 clinical trials. EBioMedicine . 2023 Jul;93:104662. doi: 10.1016/j.ebiom.2023.104662.
• Grimaldi L, Papeix C, Hamon Y, et al. Vaccines and the risk of hospitalization for multiple sclerosis flare-ups. JAMA Neurol . Published online September 5, 2023. doi:10.1001/jamaneurol.2023.2968.
• Khodaie F, Moghadasi AN, Kazemi AH, Zhao B. Effectiveness of acupuncture for fatigue in patients with relapsing-remitting multiple sclerosis: a randomized controlled trial. Acupunct Med . 2023;41(4):199-205.
• Nicholas J, Lublin F, Klineova S, et al. Efficacy of nabiximols oromucosal spray on spasticity in people with multiple sclerosis: Treatment effects on Spasticity Numeric Rating Scale, muscle spasm count, and spastic muscle tone in two randomized clinical trials. Mult Scler Relat Disord . 2023;75.104745. doi.org/10.1016/j.msard.2023.104745.

For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154 . Questions to MSAA’s Client Services department may also be emailed to [email protected] .

Written by Tom Garry, Medical Writer Reviewed by Dr. Barry Hendin, MSAA Chief Medical Officer Edited by Susan Wells Courtney, MSAA Senior Writer

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Multiple sclerosis: New biomarker confirmed for early diagnosis

A study conducted by researchers from the Department of Neurology at MedUni Vienna and University Hospital Vienna has demonstrated for the first time that diagnosis of multiple sclerosis (MS) can be significantly improved by additionally measuring the thickness of retinal layers in the eye. Use of the procedure, which is already available at the Departments of MedUni Vienna and University Hospital Vienna, helps to detect the condition at an earlier stage and predict its progression more accurately. This can lead to a decisive increase in the chance of improved patient outcomes. The findings have been published in the journal Neurology .

As part of their investigation, the research team headed by Gabriel Bsteh and Thomas Berger of the Department of Neurology at MedUni Vienna and University Hospital Vienna collaborated with colleagues from MedUni Vienna and University Hospital Vienna's Department of Ophthalmology and Optometrics to examine 267 MS patients over a period of five years. Their research built on study results published in 2022, which showed that MS relapse-related damage to the retina reflects the degree of damage caused to the patient's brain. The previous study also demonstrated that a 5 micrometre (µm) reduction in the thickness of the retinal layer following optic neuritis indicated a doubling of the risk of permanent disability after the next relapse. Thanks to the latest research with the large cohort of MS patients, the research team has confirmed that the thickness of the retinal layer can be used as a precise biomarker to assist early diagnosis.

Diagnostic procedure already available

The researchers used a procedure known as optical coherence tomography (OCT) to measure the thickness of the retinal layer. An imaging method that uses infrared light, OCT allows for the generation of high-resolution, three-dimensional images of extremely thin layers of tissue measuring just a few micrometres (1 µm is 1/1,000th of a millimetre). OCT is also a tool for diagnosing and evaluating the progression of eye diseases such as glaucoma. "So we already have this procedure at our disposal," commented Gabriel Bsteh, first author of the study. He added: "If we use optical coherence tomography alongside the current criteria to diagnose MS, we obtain significantly more accurate results at a much earlier stage. This means we can initiate treatment measures sooner, which considerably improves the long-term prognosis for patients."

Retina as a window on the brain

Multiple sclerosis is an autoimmune, chronic inflammatory disease that causes inflammation and loss of nerve cells throughout the nervous system. For the most part, patients are unable to feel the consequences of this damage to begin with, so the condition often goes undiagnosed until a late stage, meaning that valuable time is lost during which effective treatment could have been administered. Given that early detection and prognosis of the disease's progression play a decisive role in MS cases, medical researchers have been trying to find improved detection methods for some time now to help avert serious consequences such as impaired mobility and blindness as far as possible. "We have identified a new biomarker for MS diagnosis, namely the retinal layer thickness, which can be likened to a window to the brain," said Gabriel Bsteh, summing up the study's key finding. In the next phases of research, the focus will turn to the importance of retinal layer thickness in measuring responses to MS treatment.

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Materials provided by Medical University of Vienna . Note: Content may be edited for style and length.

Journal Reference :

• Gabriel Bsteh, Harald Hegen, Patrick Altmann, Michael Auer, Klaus Berek, Franziska Di Pauli, Barbara Kornek, Nik Krajnc, Fritz Leutmezer, Stefan Macher, Paulus Stefan Rommer, Karin Zebenholzer, Gudrun Zulehner, Tobias Zrzavy, Florian Deisenhammer, Berthold Pemp, Thomas Berger. Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for MS . Neurology , 2023; 10.1212/WNL.0000000000207507 DOI: 10.1212/WNL.0000000000207507

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Multiple Sclerosis

What is multiple sclerosis.

Multiple sclerosis (MS) is the most common disabling neurological disease of young adults with symptom onset generally occurring between the ages of 20 to 40 years.

In MS, the immune system cells that normally protect us from viruses, bacteria, and unhealthy cells mistakenly attack myelin in the central nervous system (brain, optic nerves, and spinal cord). Myelin is a substance that makes up the protective sheath (myelin sheath) that coats nerve fibers (axons).

MS is a chronic disease that affects people differently. A small number of people with MS will have a mild course with little to no disability, whereas others will have a steadily worsening disease that leads to increased disability over time. Most people with MS, however, will have short periods of symptoms followed by long stretches of relative quiescence (inactivity or dormancy), with partial or full recovery. The disease is rarely fatal and most people with MS have a normal life expectancy.

Myelin and the immune system

MS attacks axons in the central nervous system protected by myelin, which are commonly called white matter. MS also damages the nerve cell bodies, which are found in the brain's gray matter, as well as the axons themselves in the brain, spinal cord, and optic nerves that transmit visual information from the eye to the brain. As the disease progresses, the outermost layer of the brain, called the cerebral cortex, shrinks in a process known as cortical atrophy.

The term multiple sclerosis refers to the distinctive areas of scar tissue (sclerosis—also called plaques or lesions) that result from the attack on myelin by the immune system. These plaques are visible using magnetic resonance imaging (MRI). Plaques can be as small as a pinhead or as large as a golf ball.

The symptoms of MS depend on the severity of the inflammatory reaction as well as the location and extent of the plaques, which primarily appear in the brain stem, cerebellum (involved with balance and coordination of movement, among other functions), spinal cord, optic nerves, and the white matter around the brain ventricles (fluid-filled cavaties).

Signs and symptoms of MS

The natural course of MS is different for each person, which makes it difficult to predict. The onset and duration of MS symptoms usually depend on the specific type but may begin over a few days and go away quickly or develop more slowly and gradually over many years.

There are four main types of MS, named according to the progression of symptoms over time:

• Relapsing-remitting MS—Symptoms in this type come in the form of attacks. In between attacks, people recover or return to their usual level of disability. When symptoms occur in this form of MS, it is called an attack, a relapse, or exacerbation. The periods of disease inactivity between MS attacks are referred to as remission. Weeks, months, or even years may pass before another attack occurs, followed again by a period of inactivity. Most people with MS are initially diagnosed with this form of the disease.
• Secondary-progressive MS—People with this form of MS usually have had a previous history of MS attacks but then start to develop gradual and steady symptoms and deterioration in their function over time. Most individuals with severe relapsing-remitting MS may go on to develop secondary progressive MS if they are untreated.
• Primary-progressive MS—This type of MS is less common and is characterized by progressively worsening symptoms from the beginning with no noticeable relapses or exacerbations of the disease, although there may be temporary or minor relief from symptoms.
• Progressive-relapsing MS—The rarest form of MS is characterized by a steady worsening of symptoms from the beginning with acute relapses that can occur over time during the disease course.

There are some rare and unusual variants of MS, such as:

• Marburg variant MS (also known as malignant MS) causes swift and relentless symptoms and decline in function, and may result in significant disability or even death shortly after disease onset.
• Balo's concentric sclerosis causes concentric rings of myelin destruction that can be seen on an MRI and is another variant type of MS that can progress rapidly.

Early MS symptoms often include:

• Vision problems such as blurred or double vision, or optic neuritis, which causes pain with eye movement and rapid vision loss
• Muscle weakness, often in the hands and legs, and muscle stiffness accompanied by painful muscle spasms
• Tingling, numbness, or pain in the arms, legs, trunk, or face
• Clumsiness, especially difficulty staying balanced when walking
• Bladder control problems
• Intermittent or constant dizziness

MS may also cause later symptoms, such as:

• Mental or physical fatigue which accompanies the early symptoms during an attack
• Mood changes such as depression or difficulty with emotional expression or control
• Cognitive dysfunction—problems concentrating, multitasking, thinking, learning, or difficulties with memory or judgment

Muscle weakness, stiffness, and spasms may be severe enough to affect walking or standing. In some cases, MS leads to partial or complete paralysis and the use of a wheelchair is not uncommon, particularly in individuals who are untreated or have advanced disease. Many people with MS find that weakness and fatigue are worse when they have a fever or when they are exposed to heat. MS exacerbations may occur following common infections.

Pain is rarely the first sign of MS but pain often occurs with optic neuritis and trigeminal neuralgia, a disorder that affects one of the nerves that provides sensation to different parts of the face. Painful limb spasms and sharp pain shooting down the legs or around the abdomen can also be symptoms of MS.

Conditions associated with MS

• Transverse myelitis (an inflammation of the spinal cord) may develop in those with MS. Transverse myelitis can affect spinal cord function over several hours to several weeks before partial or complete recovery. It usually begins as a sudden onset of lower back pain, muscle weakness, abnormal sensations in the toes and feet, or difficulties with bladder control or bowel movements. This can rapidly progress to more severe symptoms, including arm and/or leg paralysis. In most cases, people recover at least some function within the first 12 weeks after an attack begins.
• Neuromyelitis optica is a disorder associated with transverse myelitis as well as optic nerve inflammation (also known as optic neuritis). People with this disorder usually have abnormal antibodies (proteins that normally target viruses and bacteria) against a specific channel in optic nerves, the brain stem or spinal cord, called the aquaporin-4 channel. These individuals respond to certain treatments, which are different than those commonly used to treat MS.
• Trigeminal neuralgia is a chronic pain condition that causes sporadic, sudden burning or shock-like facial pain. The condition is more common in young adults with MS and is caused by lesions in the brain stem, the part of the brain that controls facial sensation.

Who is more likely to get multiple sclerosis?

Females are more frequently affected than males.  Researchers are looking at several possible explanations for why the immune system attacks central nervous system myelin, including:

• Fighting an infectious agent (e.g., a virus) that has components that mimic components of the brain (molecular mimicry)
• Destroying brain cells because they are unhealthy
• Mistakenly identifying normal brain cells as foreign

There is also something known as the blood-brain barrier, which separates the brain and spinal cord from the immune system. If there is a break in this barrier, it exposes the brain to the immune system. When this happens, the immune system may misinterpret structures in the brain, such as myelin, as “foreign.”

Research shows that genetic vulnerabilities combined with environmental factors may cause MS.

Genetic susceptibility

MS itself is not inherited, but susceptibility to MS may be inherited. Studies show that some individuals with MS have one or more family member or relative who also have MS.

Current research suggests that dozens of genes and possibly hundreds of variations in the genetic code (gene variants) combine to create vulnerability to MS. Some of these genes have been identified, and most are associated with functions of the immune system. Many of the known genes are similar to those that have been identified in people with other autoimmune diseases as type 1 diabetes, rheumatoid arthritis, or lupus.

Infectious factors and viruses

Several viruses have been found in people with MS, but the virus most consistently linked to the development of MS is the Epstein-Barr virus (EBV) which causes infectious mononucleosis.

Only about five percent of the population has not been infected by EBV. These individuals are at a lower risk for developing MS than those who have been infected. People who were infected with EBV in adolescence or adulthood, and who therefore develop an exaggerated immune response to EBV, are at a significantly higher risk for developing MS than those who were infected in early childhood. This suggests that it may be the type of immune response to EBV that may lead to MS, rather than EBV infection itself. However, there is still no proof that EBV causes MS and the mechanisms that underlie this process are poorly understood.

Environmental factors

Several studies indicate that people who spend more time in the sun and those with relatively higher levels of vitamin D are less likely to develop MS or have a less severe course of disease and fewer relapses. Bright sunlight helps human skin produce vitamin D. Researchers believe that vitamin D may help regulate the immune system in ways that reduce the risk of MS or autoimmunity in general. People from regions near the equator, where there is a great deal of bright sunlight, generally have a much lower risk of MS than people from temperate areas such as the U.S. and Canada.

Studies have found that people who smoke are more likely to develop MS and have a more aggressive disease course. Indeed, people who smoke tend to have more brain lesions and brain shrinkage than non-smokers. 

How is multiple sclerosis diagnosed and treated?

Diagnosing MS

There is no single test used to diagnose MS. The disease is confirmed when symptoms and signs develop and are related to different parts of the nervous system at more than one interval and after other alternative diagnoses have been excluded.

Doctors use different tests to rule out or confirm the diagnosis. In addition to a complete medical history, physical examination, and a detailed neurological examination, a doctor may recommend:

• MRI scans of the brain and spinal cord to look for the characteristic lesions of MS. A special dye or contrast agent may be injected into a vein to enhance brain images of the active MS lesions.
• Lumbar puncture (sometimes called a spinal tap) to obtain a sample of cerebrospinal fluid and examine it for proteins and inflammatory cells associated with the disease. Spinal tap analysis also can rule out diseases that may look like MS.
• Evoked potential tests, which use electrodes placed on the skin and painless electric signals to measure how quickly and accurately the nervous system responds to stimulation.

Treating MS

There is no cure for MS, but there are treatments that can reduce the number and severity of relapses and delay the long-term disability progression of the disease.

• Corticosteroids, such as intravenous (infused into a vein) methylprednisolone, are prescribed over the course of three to five days. Intravenous steroids quickly and potently suppress the immune system and reduce inflammation. They may be followed by a tapered dose of oral corticosteroids. Clinical trials have shown that these drugs hasten recovery from MS attacks, but do not alter the long-term outcome of the disease.
• Plasma exchange (plasmapheresis) can treat severe flare-ups in people with relapsing forms of MS who do not have a good response to methylprednisolone. Plasma exchange involves taking blood out of the body and removing components in the blood's plasma that are thought to be harmful. The rest of the blood, plus replacement plasma, is then transfused back into the body. This treatment has not been shown to be effective for secondary progressive or chronic progressive MS.

Disease-modifying treatments

Current therapies approved by the U.S. Food and Drug Administration (FDA) for MS are designed to modulate or suppress the inflammatory reactions of the disease. They are most effective for relapsing-remitting MS at early stages of the disease.

Injectable medications include:

• Beta interferon drugs are among the most common medications used to treat MS. Interferons are signaling molecules that regulate immune cells. Potential side effects of these drugs include flu-like symptoms (which usually fade with continued therapy), depression, or elevation of liver enzymes. Some individuals will notice a decrease in the effectiveness of the drugs after 18 to 24 months of treatment. If flare-ups occur or symptoms worsen, doctors may switch treatment to alternative drugs.
• Glatiramer acetate changes the balance of immune cells in the body, but how it works is not entirely clear. Side effects are usually mild and consist of local injection site reactions or swelling.

Infusion treatments include:

• Natalizumab is administered intravenously once a month. It works by preventing cells of the immune system from entering the brain and spinal cord. It is very effective but is associated with an increased risk of a serious and potentially fatal viral infection of the brain called progressive multifocal leukoencephalopathy (PML). Natalizumab is generally recommended only for individuals who have not responded well to or who are unable to tolerate other first-line therapies.
• Ocrelizumab is administered intravenously every six months and treats adults with relapsing or primary progressive forms of MS. It is the only FDA-approved disease-modifying therapy for primary-progressive MS. The drug targets the circulating immune cells that produce antibodies, which also play a role in the formation of MS lesions. Side effects include infusion-related reactions and increased risk of infections. Ocrelizumab may increase the risk of cancer as well.
• Alemtuzumab is administered for five consecutive days followed by three days of infusions one year later. It targets proteins on the surface of immune cells. Because this drug increases the risk of autoimmune disorders it is recommended for those who have had inadequate responses to two or more MS therapies.
• Mitoxantrone, which is administered intravenously four times a year, has been approved for especially severe forms of relapsing-remitting and secondary progressive MS. Side effects include the development of certain types of blood cancers in up to one percent of those with MS, as well as with heart damage. This drug should be considered as a last resort to treat people with a form of MS that leads to rapid loss of function and for whom other treatments did not work.

Oral treatments include:

• Fingolimod is a once-daily medication that reduces the MS relapse rate in adults and children. It is the first FDA-approved drug to treat MS in adolescents and children ages 10 years and older. The drug prevents white blood cells called lymphocytes from leaving the lymph nodes and entering the blood, brain, and spinal cord. Fingolimod may result in a slow heart rate and eye problems when first taken. Fingolimod can also increase the risk of infections, such as herpes virus infections, or in rare cases be associated with PML.
• Dimethyl fumarate is a twice-daily medication used to treat relapsing forms of MS. Its exact mechanism of action is not currently known. Side effects of dimethyl fumarate are flushing, diarrhea, nausea, and lowered white blood cell count. 
• Teriflunomide is a once-daily medication that reduces the rate of proliferation of activated immune cells. Teriflunomide side effects can include nausea, diarrhea, liver damage, and hair loss.
• Cladribine is administered as two courses of tablets about one year apart. Cladribine targets certain types of white blood cells that drive immune attacks in MS. The drug may increase the risk of developing cancer and should be considered for individuals who have not responded well to other MS treatments.
• Diroximel fumarate is a twice-daily drug similar to dimethyl fumarate (brand name Tecfidera) but with fewer gastrointestinal side effects. Scientists suspect these drugs, which have been approved to treat secondary progressive MS, reduce damage to the brain and spinal cord by making the immune response less inflammatory, although their exact mechanism of action is poorly understood.
• Siponimod tablets (Mayzent) is taken orally and has a similar mechanism of action to fingolimod. Siponimod has been approved by the FDA to treat secondary-progressive MS.

Clinical trials have shown that cladribine, diroximel fumarate, and dimethyl fumarate decrease the number of relapses, delay the progress of physical disability, and slow the development of brain lesions.

Managing MS symptoms

MS causes a variety of symptoms that can interfere with daily activities but can usually be treated or managed. Many of these issues are best treated by neurologists who have advanced training in the treatment of MS and who can prescribe specific medications to treat these problems.

Eye and vision problems are common in people with MS but rarely result in permanent blindness. Inflammation of the optic nerve (optic neuritis) or damage to the myelin that covers the nerve fibers in the visual system can cause blurred or grayed vision, temporary blindness in one eye, loss of normal color vision, depth perception, or loss of vision in parts of the visual field. Uncontrolled horizontal or vertical eye movements (nystagmus), “jumping vision" (opsoclonus), and double vision (diplopia) are common in people with MS. Intravenous steroid medications, special eyeglasses, and periodically resting the eyes may be helpful.

Muscle weakness and spasticity is common in MS. Mild spasticity can be managed by stretching and exercising muscles using water therapy, yoga, or physical therapy. Medications such as gabapentin or baclofen can reduce spasticity. It is very important that people with MS stay physically active because physical inactivity can contribute to worsening stiffness, weakness, pain, fatigue, and other symptoms.

Tremor, or uncontrollable shaking, develops in some people with MS. Assistive devices and weights attached to utensils or even limbs are sometimes helpful for people with tremor. Deep brain stimulation and drugs, such as clonazepam, may also be useful.

Problems with walking and balance occur in many people with MS. The most common walking problem is ataxia—unsteady, uncoordinated movements—due to damage to the areas of the brain that coordinate muscle balance. People with severe ataxia generally benefit from the use of a cane, walker, or other assistive device. Physical therapy also can reduce walking problems. The FDA has approved the drug dalfampridine to improve walking speed in people with MS.

Fatigue is a common symptom of MS and may be both physical (tiredness in the arms or legs) and cognitive (slowed processing speed or mental exhaustion). Daily physical activity programs of mild to moderate intensity can significantly reduce fatigue, although people should avoid excessive physical activity and minimize exposure to hot weather conditions or ambient temperature. Other drugs that may reduce fatigue include amantadine, methylphenidate, and modafinil. Occupational therapy can help people learn how to walk using an assistive device or in a way that saves physical energy. Stress management programs, relaxation training, membership in an MS support group, or individual psychotherapy may help some people.

Pain from MS can be felt in different parts of the body. Trigeminal neuralgia (facial pain) is treated with anticonvulsant or antispasmodic drugs, or less commonly, painkillers. Central pain, a syndrome caused by damage to the brain and/or spinal cord, can be treated with gabapentin and nortriptyline. Treatments for chronic back or other musculoskeletal pain may include heat, massage, ultrasound, and physical therapy.

Problems with bladder control and constipation may include urinary frequency, urgency, or the loss of bladder control. A small number of individuals retain large amounts of urine. Medical treatments are available for bladder-related problems. Constipation is also common and can be treated with a high-fiber diet, laxatives, and stool softeners.

Sexual dysfunction can result from damage to nerves running through the spinal cord. Sexual problems may also stem from MS symptoms such as fatigue, cramped or spastic muscles, and psychological factors. Some of these problems can be corrected with medications. Psychological counseling may be helpful.

Clinical depression is frequent among people with MS. MS may cause depression as part of the disease process and chemical imbalance in the brain. Depression can intensify symptoms of fatigue, pain, and sexual dysfunction. It is most often treated with cognitive behavioral therapy, and selective serotonin reuptake inhibitor (SSRI) antidepressant medications, which are less likely than other antidepressant medications to cause fatigue.

Inappropriate and involuntary expressions of laughter, crying, or anger—symptoms of a condition called pseudobulbar affect—sometimes are associated with MS. These expressions are often incongruent with mood; for example, people with MS may cry when they are actually happy or laugh when they are not especially happy. The combination treatment of the drugs dextromethorphan and quinidine can treat pseudobulbar affect, as can other drugs such as amitriptyline or citalopram.

Cognitive impairment—a decline in the ability to think quickly and clearly and to remember easily—affects up to 75 percent of people with MS. These cognitive changes may appear at the same time as the physical symptoms or they may develop gradually over time. Drugs such as donepezil may be helpful in some cases.

Complementary and alternative therapies

Many people with MS benefit from complementary or alternative approaches such as acupuncture, aromatherapy, ayurvedic medicine, touch and energy therapies, physical movement disciplines such as yoga and tai chi, herbal supplements, and biofeedback.

Because of the risk of interactions between alternative and conventional therapies, people with MS should discuss all the therapies they are using with their doctor, especially herbal supplements. Herbal supplements have biologically active ingredients that could have harmful effects on their own or interact harmfully with other medications.

What are the latest updates on multiple sclerosis?

The National Institute of Neurological Disorders and Stroke ( NINDS ), a component of the National Institutes of Health ( NIH ), is the leading federal funder of research on the brain and nervous system, including research on MS.

In addition to NINDS , other NIH Institutes—including the National Institute of Allergy and Infectious Diseases ( NIAID )—fund research on multiple sclerosis. Find more information on NIH research efforts through  NIH RePORTER , a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and patents citing support from these projects.

Although researchers have not been able to identify the cause of MS with any certainty, there has been excellent progress in other areas of MS research—especially in the development of new treatments to prevent exacerbations of the disease. New discoveries are constantly changing MS treatment options and helping to reduce MS-related disability.

Research projects conducted by NINDS scientists or through NIH grants to universities and other sites across the U.S. cover a wide range of topics such as comorbidities, mechanisms of cognitive impairment, blood-brain barrier breakdown in MS, the role of sleep and circadian rhythms, rehabilitation strategies, and telehealth. Other topics include:

• Biomarkers to accurately diagnose MS and monitor disease progression, including blood and imaging tests (e.g., MRI)
• Genetic and environmental risk factors for MS, such as low Vitamin D or the Epstein-Barr virus
• The role of the gut microbiome and diet in MS
• Mechanisms that underlie gender differences in the incidence and presentation of MS
• MS risk factors and disease course in African American and Hispanic populations, and disparities in care
• The role of the immune system in MS, including its function in the central nervous system (CNS)
• The role and crosstalk of various cell types in the CNS with relation to MS
• Basic functions of myelination, demyelilnation, and axonal degeneration, and strategies to overcome axonal and myelin loss

Scientists sponsored by  NIAID are testing an experimental stem cell treatment titled, autologous hematopoietic stem cell transplantation (AHSCT), against the best available biologic therapies for severe forms of relapsing MS.

Investigators in the clinical trial  BEAT-MS (BEst Available Therapy versus autologous hematopoietic stem cell transplant for Multiple Sclerosis)  are removing some immune cells and then infusing some of the person's own blood-forming stem cells to reset the immune system so it no longer attacks the CNS. 

Genetic research funded by NINDS is exploring the roles of "susceptibility genes"—genes that are associated with an increased risk for MS. Several candidate genes have been identified and researchers are studying their function in the nervous system to discover how they may lead to the development of MS.

Other studies aim to develop better neuroimaging tools, such as more powerful MRI methods, to diagnose MS, track disease progression, and assess treatments. NINDS scientists are collecting MRIs of the brain and spinal cord and scans of the retina, along with other clinical and biological data, from more than 100 individuals with MS and 50 individuals without the disease over a period of years to observe changes in the course of MS. Investigators are using MRI to study the natural history of MS and to help define the mechanism of action and cause of side effects of disease modifying therapies.

Intramural research programs on MS

NINDS and other NIH Institutes have a very active MS intramural research program among scientists working at NIH. Together, they  have:

• Established and continue to develop MRI as a critical tool for examining the natural course of the disease in humans, monitoring disease progression, assessing effects of treatments in clinical trials, and understanding MS biology
• Played an important role in understanding why some patients develop a rare and potentially fatal brain infection (progressive multifocal leukoencephalopathy) when taking potent MS drugs, and they are developing new treatments for this infection
• Unraveled mechanisms by which viruses, especially the Epstein-Barr virus, contribute to the development of MS
• Conducted next-generation treatment trials targeting specific mechanisms of disease progression, using advanced MRI and fluid biomarkers as outcome measures
• Developed the first MRI method to visualize the lymph vessels surrounding the brain, which play a critical role in neuro-immune communication

Translational research

NIH supports translational studies to develop therapies that will stop or reverse the course of the disease, focusing on pathways that modify immune system function, repair damaged myelin, or protect neurons from damage. Researchers are also developing animal models of MS to more accurately predict drug response in human disease. However, current animal models share some of the disease mechanisms and symptoms of MS but do not fully mimic the disease, especially in its clinically progressive phase.

Focus on progressive MS therapies

Scientists continue to study the biology and mechanisms of relapsing-remitting MS while increasing efforts to stop or prevent the steady decline in function that occurs in progressive MS. In the MS-SPRINT trial, the NINDS NeuroNEXT clinical trials network tested the drug ibudilast as a potential neuroprotective drug for progressive MS and showed that the drug slowed the rate of brain shrinkage as compared to a placebo. NINDS Intramural scientists are conducting proof-of-concept clinical trials to address a key driver of clinical progression called the “slowly expanding lesion.”

Focus on biomarkers

As part of a larger effort to develop and validate effective biomarkers (signs that may indicate risk of a disease or be used to monitor its progression) for neurological disease, NINDS is supporting two definitive multicenter MS studies:

• The Central Vein Sign in MS (CAVS-MS) study, which is testing whether a rapid MRI approach designed by NINDS Intramural scientists can use the detection of a central vein passing through brain plaques to differentiate MS from other common neurological disorders that can mimic MS. The goal is to develop a reliable imaging test for MS in order to achieve rapid yet accurate diagnosis and reduce misdiagnosis, which may affect up to 20 percent of people currently diagnosed with MS.
• A study to test whether a simple new blood test that measures small amounts of neuron-derived proteins (neurofilaments) can be used to predict the severity of disease and help determine whether MS drugs are working to protect brain tissues.

How can I or my loved one help improve care for people with multiple sclerosis?

Consider participating in a clinical trial so clinicians and scientists can learn more about MS and related disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are needed— those who are healthy or may have an illness or disease— of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You . Learn about clinical trials currently looking for people with MS at Clinicaltrials.gov .

Where can I find more information about multiple sclerosis? Information may be available from the following organizations and resources: Accelerated Cure Project for Multiple Sclerosis Phone: 781-487-0008 Autoimmune Association Phone: 586-776-3900  Multiple Sclerosis Association of America (MSAA) Phone: 856-488-4500 or 800-532-7667 Multiple Sclerosis Foundation (MS Focus) Phone: 954-776-6805 or 888 673-6287 Myelin Repair Foundation (MRF) Phone: 408-871-2410 National Ataxia Foundation (NAF) Phone: 763-553-0020 National Multiple Sclerosis Society Phone: 800-344-4867 National Organization for Rare Disorders (NORD) Phone: 203-744-0100 National Rehabilitation Information Center (NARIC) Phone: 301-459-5900 or 800-346-2742; 301-459-5984 Paralyzed Veterans of America Phone: 202-872-1300 or 800-555-9140

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Leveling the field: MSU researcher develops new, affordable detection and monitoring methods for cardiovascular disease

Contact: Aspen Harris

STARKVILLE, Miss.—A Mississippi State University researcher is developing new, more affordable methods for early detection and monitoring of cardiovascular disease, the leading cause of death in the U.S.

Amirtahà Taebi, assistant professor of biomedical engineering, is using the human body’s vibrations to develop noninvasive diagnosis methods for cardiovascular disease using smartphones and low-cost sensors with a focus on health equity in the Taebi Lab at MSU. Work in the lab is directed toward low-income populations and underrepresented minorities, those usually more affected.

“One American dies from a cardiovascular disease every 34 seconds,” Taebi said. “If you place your hand on your chest, you will feel vibrations as a result of your heart pumping blood to different organs in your body. We can measure those vibrations using sensors.”

The lab is studying these cardiovascular-induced vibrations to see what cardiovascular events are represented by each vibration waveform.

He said that by analyzing the heart’s vibrations, his team aims to address questions regarding heart function and detect any signs of cardiovascular disease in people who may need medical attention.

The ultimate goal of Taebi and his team is to reduce mortality rates, optimize medical therapy, reduce hospital stays and improve the lives of patients.

In an effort to improve health equity, the lab is developing a more accessible method for cardiovascular activity monitoring through a smartphone app. Another project involves creating a low-cost heart monitor that individuals can keep at home to monitor different aspects of cardiovascular activities, including the electrical and mechanical aspects, blood oxygen levels and heart sounds.

“Mississippi has the second highest mortality rate in the country from congenital heart diseases, for example,” Taebi said. “That’s why we want to create methods that are accessible, low-cost and widely available to the general public for cardiovascular monitoring, so even those in rural areas and low-income individuals can afford to use these devices to monitor their own or their loved one’s cardiovascular activity. If something is wrong, they can know as soon as possible and see a doctor to determine their next steps.”

Before joining MSU in 2021, Taebi completed his postdoctoral fellowship in the biomedical engineering department at the University of California, Davis. He received a doctorate in mechanical engineering from the University of Central Florida, a master’s in biomedical engineering at Politecnico di Milano in Italy and a bachelor’s in mechanical engineering from Sharif University of Technology in Iran.

For more on MSU’s Department of Agricultural and Biological Engineering, visit www.abe.msstate.edu/ .

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Dynamic headspace GC-MS method to detect volatile extractables from medical device materials

2023 FDA Science Forum

Volatile extractables, released from medical devices during use, are a concern as they may expose patients to harmful levels of toxic compounds.  According to ISO 10993-18:2020, the Analytical Evaluation Threshold (AET) is used to determine the analytical sensitivity required to detect extractables from medical devices. Compounds, at or above the AET, need to be reported for toxicological risk assessment. Currently, volatile analysis by static headspaces is used as a supplementary technique for medical device or material extracts. Variation of signal response in static headspace led to undefined AET for the volatile analysis method. Therefore, investigating new technologies that generate reproducible data for volatile quantification is needed for improved hazards identification. This study was designed to evaluate the performance of dynamic headspace (DHS) gas chromatography-mass spectrometric (GC-MS) analysis to achieve the sensitivity levels suitable for proper toxicological risk assessment for volatiles extracted from medical devices.  DHS method development was conducted using residual solvents class 3 - mix A standard and the initial method development and analyses were done using GERSTEL MPS attached to Agilent GC-MS system. Two different methods were designed to address both volatile and semi volatile compounds. The efficiency of DHS extraction was optimized based on incubation temperature, trapping volume/ time, adsorbent type (Carbopack B/ Carbopack X (Carbopack B/X) and Tenax TA), and drying time for low volume samples. Method performance was compared with commonly used static headspace GC-MS analysis. To further improve the headspace concentration of more water-soluble compounds such as alcohols, and ketones, the effect of surfactants addition to the sample matrix was also investigated. Application of developed methods were tested using saline extracts of various medical device materials such as ABS, Buna and PVC.  Preliminary results showed improved efficiency in detecting volatile extractable in ABS material extracts with semi volatile method with increased peak area responses compared to the volatile method. This sensitive dynamic headspace GC-MS method may facilitate improved toxicological risk assessment for the volatiles detected in medical devices. 

Download the Poster (PDF; 2.24 MB)