Multiple Sclerosis (MS)

Understanding Multiple Sclerosis

It’s still not clear why some people develop multiple sclerosis (MS), which is a type of autoimmune disease. With any autoimmune disease, the body’s immune system becomes confused and no longer differentiates between invading germs it should fight and the body’s own healthy cells, tissues, and organs. So the immune system attacks normal structures within the body. There are more than 80 different autoimmune diseases that have been identified. The National Institutes of Health (NIH) estimates that more than 23.5 million Americans have an autoimmune disease, and the prevalence of many of these diseases is rising, likely due to environmental causes that have yet to be completely explained (NIH, 2012; Schmidt, 2011).

MS is characterized by the immune system attacking the central nervous system, specifically targeting myelin and nerve fibers. Myelin is the protective sheath made of fats and proteins that covers nerves and facilitates the efficient transmission of nerve signals. When the myelin and nerve fibers become damaged, nerves lose their function and the neurological symptoms of MS occur. These areas of damage or scarring in the central nervous system are called lesions.

Symptoms of Multiple Sclerosis

Myelin and nerve fiber damage cause neurological symptoms such as weakness, numbness, pain, cramping, muscle spasms, loss of balance, pins-and-needles feelings, and paralysis. Symptoms of MS are unpredictable and highly variable from person to person. People may also experience any of the following symptoms (or others): head pain, muscle tremor, fatigue, dizziness, reduced sensation, urinary incontinence, blurred vision, sexual dysfunction, anxiety, and difficulty speaking. Most people with MS have a near-normal life expectancy.

Subtypes of Multiple Sclerosis

The majority of people with MS have what’s called relapsing-remitting MS (RRMS), in which symptoms repeatedly relapse then improve or go away completely. Most people with RRMS will eventually develop secondary-progressive MS (SPMS), in which symptoms progressively worsen, no longer with any recovery, which causes issues with walking or, eventually, loss of neurological function. Others may not experience any relief periods, instead following an accelerated disease course—this is called primary-progressive MS (PPMS).

Types of MS can be further characterized by whether they are active (relapsing or new lesions as detected by MRI), not active, worsening (an increase in disability after a relapse), or not worsening. Some people may have an episode of MS-like neurological issues related to inflammation and demyelination of the nervous system that lasts 24 hours or more, which is called clinically isolated syndrome (CIS). People with CIS may or may not go on to develop MS.

Potential Causes of Multiple Sclerosis

While the exact cause of MS is not completely understood, there are various theories related to the immune system, infections, and genetics. MS is associated with smoking, obesity, and low vitamin D levels. MS also tends to affect communities in clusters.

Immunologic Causes

The nervous system inflammation that is characteristic of MS is likely caused by an abnormal immune response. The two key players in immune function are T cells, which cause inflammation, and B cells, which produce antibodies and cause central nervous system damage. However, it’s not clear what causes abnormal T and B cell activity to set the processes behind MS into motion.

Consuming cow’s milk has been linked to prevalence of MS since the 1970s, and recent research has begun to explain how milk could trigger an autoimmune response contributing to or aggravating MS in some people. Autoimmunity occurs when a structure in the body is mistakenly attacked by antibodies. In this case it appears that antibodies to casein, one of the proteins in milk, may also bind to a protein in the myelin sheath protecting nerves. Most people do not make antibodies to milk proteins, but some do for poorly understood reasons. When these antibodies bind to myelin, they could initiate or aggravate demyelination. Researchers from several universities in Germany and from Stanford University School of Medicine suggest that patients with antibodies to casein may benefit from restricting dairy products in their diets (Chunder et al, 2022).

Viruses

Several studies have linked the Epstein-Barr virus, human herpes virus 6, and other viral infections to MS development. The theory is that these viruses infect immune cells, which predisposes the body to autoimmunity (Ascherio & Munger, 2016).

Genetic Susceptibility

There is a genetic risk associated with MS. If one identical twin has MS, the other twin has a one in four chance of developing it, too. There is a lesser, but still high, risk of developing MS if one of your parents or nonidentical siblings has the disease.

MS Clusters

MS clusters—a higher-than-statistically-expected number of MS diagnoses—in certain regions have been reported over the years. Because MS is caused by a complex interplay of environmental and genetic factors, it’s possible that individuals who live in the same area may be exposed to the same combination of risk factors that can trigger MS development, such as cigarette smoking, obesity, infection with Epstein-Barr virus, and low vitamin D status (Ascherio & Munger, 2016). Researchers have looked into reports of clusters over the years in order to determine what unique factors in these areas may have led to MS. However, these studies are notoriously difficult to conduct as it requires retrospectively assessing people’s exposures to potential triggers from their childhood and throughout their life. There is also uncertainty about whether clusters point to any particular cause of concern or this is just normal, random statistical variation in disease onset.

How Multiple Sclerosis Is Diagnosed

MS usually occurs around age 30. The first symptoms of MS are generally vision problems or numbness of the face, body, arms, or legs. Since there is no specific test for MS and the disease can appear so differently person to person, some may be diagnosed early on, while others may have more elusive symptoms that doctors can’t easily diagnose. RRMS is usually a straightforward diagnosis based on symptoms and brain scans, which can show nerve damage early on. In more-difficult cases and for people with PPMS, blood tests and spinal fluid analyses for abnormal antibodies may be needed as well as evoked potential tests, which measure the nervous system’s response to visual or electrical stimuli.

Lifestyle Changes

Managing MS involves avoiding triggers that may cause symptoms to worsen. Various types of medical equipment can help with mobility, and caregivers can help improve quality of life and ensure safety. People with MS should avoid smoking.

Avoiding Pseudo-Relapses

When inflammation of the central nervous system damages the myelin coating of nerves, relapses can occur. Relapses will generally resolve on their own without treatment; however, severe relapses may warrant medication. Fatigue, physical activity, stress, and heat can also cause symptoms to worsen, which is known as a pseudo-relapse because the symptoms are not caused by central nervous system inflammation. If you find that these are triggers for you, avoid sun exposure and extreme temperatures. Work with your doctor to determine what level of physical activity is right for you. Additionally, you may be prescribed medications to help with relapse or associated symptoms (see the conventional treatments section).

Mobility

When muscles no longer receive the correct input from the nervous system, certain activities, such as walking, can become more difficult. Adaptive equipment can help keep you mobile. An ankle-foot orthosis is a brace that is worn over the leg and foot to support the ankle and correct foot drop (difficulty lifting the front of the foot when walking). Other mobility equipment may include supportive shoes, wheelchairs, or vehicle modifications to help with driving. Support animals may also be useful for walking, alerting people with MS to nearby sounds or danger, providing balance, and much more. Work with your health care provider and physical therapist to determine what resources are most beneficial for you and what your insurance can help cover.

Falls

A combination of mobility issues, weakness, dizziness, sensory defects, tremors, fatigue, heat intolerance, and medication side effects puts patients with MS at high risk for falls. It’s important to identify potentially dangerous areas in your home, such as the shower, toilet, or stairs, and make them safe. Discuss any specific symptoms with your doctor to determine whether they could be better managed to prevent falls. You may also find that a mobility device, such as a cane, is useful, especially if you find yourself falling often or having to hold on to furniture or walls in order to move. If you fall, try to relax and assess whether you have any injuries before you stand up. If you need help, ask someone nearby or call 911, as needed of course.

Caregivers

As MS progresses, some patients may want caregivers to help with household chores, daily tasks, or looking after them—whether in a hospital or at their home. Do you need a caregiver? If you’re having issues with things like taking a shower, it can be helpful to have someone there to help you, so you don’t fall or hurt yourself. Although it may at first seem limiting or as if you’re giving up, a reliable caregiver is very important for maintaining independence. Even if you can do regular tasks around the house alone, having a caregiver can free you up so you’re less fatigued and can spend time on the things you love.

Unfortunately, having a caregiver can be expensive as many commercial health insurance companies do not cover the cost. Long-term care policies may cover the cost. Many people with MS also rely on family members for assistance and care. This can place a significant burden on family members, causing stress and impacting quality of life. The National Multiple Sclerosis Society has an informative guide about home care providers and caring for loved ones with MS.

Smoking

Numerous studies have concluded that cigarette smokers have an increased risk of developing MS and that people with MS who smoke are more prone to accelerated disease progression (Degelman & Herman, 2017). Considering this, it’s crucial that individuals with MS quit smoking. If you need help quitting, talk to your doctor about options.

Nutrients and Supplements for Multiple Sclerosis

It’s generally recommended that people with MS supplement with vitamin D. Vitamin B12, polyunsaturated fatty acids, and antioxidants, such as resveratrol, may also be beneficial. More research is needed on calcium, selenium, and zinc for MS.

Vitamin D

Studies have shown that low vitamin D is a risk factor for MS development: People who spent more time outside as children have been shown to have a lower risk of MS (Pierrot-Deseilligny & Souberbielle, 2017). Countries farther from the equator have a higher incidence of MS (Ascherio & Munger, 2016). New research has shown that vitamin D may help protect against MS by reducing inflammation and modulating the immune system. And several studies have suggested benefits from vitamin D supplementation in MS patients (Bagur et al., 2017). So it’s recommended that individuals with MS supplement with vitamin D if they are not getting regular sun exposure (Pierrot-Deseilligny & Souberbielle, 2017).

Vitamin B12

This vitamin plays a role in the formation of the myelin sheath (the protective covering around nerves that is damaged in MS patients) as well as white blood cell production, which is crucial for immunity. So understandably it’s important for people with MS to get enough B12. Several studies have found that patients with MS have low levels of vitamin B12; however, there isn’t enough research to determine whether supplementing with vitamin B12 can reduce MS disease activity (Bagur et al., 2017). Because B12 is present only in animal foods and is difficult to absorb, a supplement is beneficial for vegans and vegetarians, as well as anyone over the age of 50, as our ability to absorb the vitamin decreases as we age (NIH, 2019b).

Polyunsaturated Fatty Acids

While some researchers hypothesize that polyunsaturated fatty acids (PUFAs) such as omega-3 fatty acids may help with neuronal function, there has been conflicting evidence on whether people with low intake of PUFAs are at higher risk for MS (NIH, 2019a). A 2017 study analyzed data from the Nurses’ Health Study, a large cohort of women who were followed from 1984 to 2004, and found that women who reported a higher intake of the omega-3 alpha-linolenic acid had a lower risk of MS. Further research is needed to confirm whether omega-3 fats are protective against MS and future clinical research should also determine whether supplementation in patients with MS is helpful for reducing disease activity.

Calcium

A mineral that is often discussed in the context of MS is calcium. It’s been reported that calcium and phosphate levels are low in individuals with MS (see the research section) (Kubicka-Baczyk, Labuz-Roszak, Pierzchala, Adamczyk-Sowa, & Machowska-Majchrzak, 2015). However, there haven’t been adequate studies to reach any conclusions about calcium levels in MS patients or whether supplementation is helpful. Calcium is important for people who are at risk for osteoporosis, as many people with MS are. Talk to your doctor about whether you need to up your calcium intake.

Selenium

Some studies have shown that people with MS may have lower levels of selenium, which has led to the suggestion that supplementing would be helpful, as selenium has antioxidant effects (Socha et al., 2014). However, adequate clinical trials have not been conducted yet.

Zinc

The research on zinc and MS has been mixed—some studies show that people with MS have low levels, whereas other studies say no, MS patients have high levels of zinc, which activate the immune system and worsen MS. The difference may be due to the whether the zinc is measured in the blood or the cerebrospinal fluid. Studies haven’t been consistent enough to come to any definitive conclusions yet, and there also haven’t been adequate studies to show whether supplementation is helpful or harmful (Bredholt & Frederiksen, 2016).

Antioxidants

Research suggests that oxidative stress (an imbalance between antioxidants and the reactive free radicals that can damage cells and tissues) may play a role in multiple sclerosis development and progression. And antioxidants have been proposed as a way to protect the brain from atrophying and to prevent some of the damage that MS causes (Gilgun-Sherki, Melamed, & Offen, 2004). Currently, there aren’t robust clinical trials to support the use of any specific antioxidant for MS-related damage. This is the evidence we have today:

1. • One study from 2017 found that SPMS patients who took 1,200 milligrams of racemic alpha lipoic acid daily for two years had less brain atrophy than those who did not take lipoic acid (Spain et al., 2017). Racemic lipoic acid is the most widely commercially available form of alpha lipoic acid, and it contains both the R isomer (found in various foods, including yeast, spinach, broccoli, and potatoes) and the S isomer (found only in synthetic material).

2. • A 2015 review found that there was promising preclinical evidence for the use of EGCG, a polyphenol found in tea, as well as for alpha lipoic acid. Both of these compounds have anti-inflammatory and antioxidant properties that may work to reduce neurological damage (Plemel et al., 2015).

3. • Other antioxidants that have demonstrated preclinical benefits include turmeric and resveratrol (Sanadgol et al., 2017).

Further robust clinical research is needed to determine which antioxidants are the most useful for patients with MS.

Resveratrol

Found in the skin of grapes and blueberries, resveratrol is a polyphenol that is celebrated for its antioxidant effects. Some research suggests that resveratrol may pass the blood-brain barrier and make its way into the brain, helping with neurological issues by decreasing inflammation. Several preclinical studies have shown that resveratrol is beneficial for mice with MS-like symptoms (Sanadgol et al., 2017). A particularly interesting 2017 study found that resveratrol promoted remyelination (regeneration of the myelin that is damaged as a result of MS) (Ghaiad, Nooh, El-Sawalhi, & Shaheen, 2017). These studies are very promising; future clinical research is needed to determine whether the effects found in mice are generalizable to humans with MS as well.

Conventional Treatments for Multiple Sclerosis

There is unfortunately no known cure for MS—yet. Treating MS involves managing attacks and symptoms, while attempting to reduce disease progression. Treatment is highly individual depending on the severity, symptoms, type of MS, and personal preferences.

Treating Severe Relapses

During a severe relapse, most neurologists recommend a course of high-dose corticosteroids for a few days to reduce inflammation. This can help lessen the duration of the attack and promote recovery. Another treatment for MS attacks is called plasma exchange: Your blood is taken, the plasma is removed, your blood cells are mixed with a protein solution, and then they are put back in your body. Plasma exchange is particularly effective for patients who have new symptoms and don’t respond well to corticosteroids (Mayo Clinic, 2019).

Disease-Modifying Drugs

These medications are intended to slow disease progression by reducing the frequency and severity of relapses and reducing brain lesions. There is only one FDA-approved disease-modifying therapy for PPMS, which is called ocrelizumab (Ocrevus). There are several disease-modifying medications approved by the FDA for relapsing forms of MS.

The standard first-line treatment for relapsing MS is IFN-beta (beta interferon), which is injected and works by reducing inflammation. In clinical trials of IFN-beta, the most common adverse side effect was depression (Watzlawik, Wootla, & Rodriguez, 2016). While taking IFN-beta, you’ll need to monitor your liver, as liver damage is also one of the side effects (Byrnes, Afdhal, Challies, & Greenstein, 2006). Another type of injectable medication is glatiramer acetate (Copaxone), which may block immune attacks against myelin. There are also oral treatments to reduce relapses, including immunosuppressants, like fingolimod and teriflunomide, as well as anti-inflammatories, like dimethyl fumarate and siponimod. (Siponimod and cladribine, a chemotherapy drug, are also approved for active SPMS treatment.) Other treatments for relapsing forms of MS are delivered by infusion, including ocrelizumab, natalizumab, alemtuzumab, and mitoxantrone (which is reserved for extremely severe cases of MS) (Mayo Clinic, 2019).

Work with your doctor to determine which medications are right for you, taking into account the significant side effects.

Symptom-Specific Treatments

Muscle relaxants may be prescribed to reduce muscle stiffness and spasms. To reduce MS-related fatigue, amantadine (a dopamine promoter and antiviral) or stimulants, such as modafinil or methylphenidate (Ritalin), may be prescribed. For people with impaired walking ability due to MS, dalfampridine (Ampyra) is the only prescription medicine used to help improve walking speed. Other medications may be needed for more specific symptoms related to the bladder, pain, mood, or sexual function (Mayo Clinic, 2019).

Physical Therapy

For patients who lose their ability to walk or talk, physical therapy can be important for regaining normal functionality. Physical therapy exercises work to strengthen muscles and improve balance and coordination; however, there has been a lack of quality research on the precise exercises and regimens that are beneficial for patients. Moderate endurance training has been shown to improve muscle strength in the arms and legs and help with walking speed, fatigue, and quality of life. Resistance training also improves muscle strength as well as walking speed and stair climbing and eases disability and fatigue. Combined endurance and resistance training may be beneficial, but which exercises and programs are right depends on the individual’s physical abilities and health (Döring, Pfueller, Paul, & Dörr, 2011).

Functional Electrical Stimulation (FES)

Another type of physiotherapy that may be used is called functional electrical stimulation (FES). FES sends weak electrical pulses through muscles in order to improve their function when the nervous system can no longer correctly send the muscle impulses. A 2017 meta-analysis of 19 studies found that FES improved foot drop (difficulty lifting the front of the foot) as well as walking speed in patients with MS (Miller et al., 2017). There are two FES devices designed to assist with foot drop, the WalkAide and the NESS L300. These devices may not be covered by insurance, so talk with your health care practitioner about the best option for you (National Multiple Sclerosis Society).

Complementary Treatment Options for Multiple Sclerosis

While regular medical care is essential for people with MS, combining medical care with complementary and alternative medicines may help improve quality of life by reducing pain and improving mood. There are plenty of options that may be worth adding to your regular care, such as psychotherapy, gentle yoga, acupuncture, herbal supplements, and cannabis.

Psychotherapy

Living with MS can be both physically and psychologically taxing. Being able to share your worries, concerns, and struggles with a licensed therapist may help release some of the stress. Depression is very common in individuals with MS—about two to three times more common than it is in the general population; whether that’s due to biological causes or living with a debilitating illness is not clear (Patten, Marrie, & Carta, 2017). Seek help if you need or want it, and find a therapist whom you feel comfortable with. They can work with you on mental obstacles and help you feel more in charge of your life. If necessary, they can also refer you to a doctor who can prescribe antidepressant medications.

Yoga

Whether it’s just to relax or to work on body mobility and flexibility, yoga is a great exercise that can be modified to be quite gentle or more intense depending on what you’re looking for. A 2014 review found that yoga may improve short-term fatigue and mood in patients with MS (Cramer, Lauche, Azizi, Dobos, & Langhorst, 2014). Work with your health care practitioner to determine your exercise needs and abilities. Start incorporating yoga slowly, and let your instructor know about relevant limitations and conditions so they can suggest pose modifications.

Whole-Body Vibration

Vibration therapy or whole-body vibration (WBV) involves standing or doing exercises on a platform that sends out oscillating vibrations. This vibration is believed to cause a person’s muscles to contract and relax frequently, which may help improve symptoms of MS and help people reap more benefits from exercise. A 2018 systematic review found that WBV could benefit patients with MS in terms of muscle strength, functioning, coordination, and balance; however, there are not many well-designed studies of WBV training effectiveness (Bueno, Ramos-Campo, & Rubio-Arias, 2018), and more research is needed in this area. Talk to your doctor or physical therapist before trying WBV.

Acupuncture

In a small study of 20 patients with RRMS, acupuncture appeared to improve patients’ scores on a test of their ability to walk 25 feet (Criado, Santos, Machado, Gonçalves, & Greten, 2017). Another study integrated acupuncture into eight group wellness sessions that were administered to women with MS. The researchers found that the women’s fatigue, stress, pain, depression, anxiety, and sleep issues decreased significantly, while their quality of life and ability to care for themselves improved significantly (Becker, Stuifbergen, Schnyer, Morrison, & Henneghan, 2017). This research points to the importance of holistic health approaches for people with MS and a possible role of acupuncture in improving symptoms.

Ginkgo

Ginkgo, a tree species that has been used as an herbal remedy in traditional Chinese medicine, has been evaluated in several clinical trials with mixed results. One small study showed that 240 milligrams of ginkgo extract daily for a month improved fatigue among 22 people with MS (Johnson et al., 2006). A small study of 38 people with MS suggested that 240 milligrams of ginkgo daily for three months may improve some aspects of cognition. However, when the same research group conducted a larger study of 120 people with MS a few years later, they found that 240 milligrams of daily ginkgo did not improve cognitive function (J. Lovera et al., 2007; J. F. Lovera et al., 2012). Other studies have assessed whether ginkgo helps reduce MS disease activity with mixed results, so further clinical research is needed to determine if and how ginkgo may be beneficial to MS patients (Mojaverrostami, Bojnordi, Ghasemi-Kasman, Ebrahimzadeh, & Hamidabadi, 2018).

Asian Ginseng

Ginseng has been researched for its ability to help with various neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, with promising findings from preclinical studies demonstrating its antioxidant and anti-inflammatory effects (Cho, 2012). The majority of clinical research has been on ginseng’s ability to enhance physical performance, and these studies have largely been done on healthy adults. One small study of people with MS showed that 250 milligrams taken twice daily for three months improved fatigue and quality of life (Etemadifar et al., 2013). Much more research is needed on ginseng for people with MS patients before recommendations for use can be made.

Cannabis

For people with MS who experience pain, muscle stiffness, or spasms, cannabis may be useful. Nabiximols, a mucosal spray that contains equal parts THC and CBD, has been used in US clinical trials of patients with MS and has been approved in some countries for MS-associated spasticity. A 2010 meta-analysis of 666 MS patients found that Sativex (a brand of nabiximols containing 2.7 milligrams of THC and 2.5 milligrams of CBD) reduced spasticity and had few side effects (Wade, Collin, Stott, & Duncombe, 2010). Smoking cannabis may also have benefits, as a small study of 30 people with MS found that those who smoked five puffs of a cannabis cigarette containing 4 percent THC had a reduction in muscle pain and spasticity (Corey-Bloom et al., 2012).

Although the clinical research is still preliminary and cannabis has not been FDA-approved for MS use, there has been momentum behind its use as it becomes legal in more states. The National Multiple Sclerosis Society supports the use of medical marijuana in states where it is legal. However, it’s important to note that there are sometimes psychological side effects associated with marijuana use in people with MS, such as cognitive impairment, and marijuana use has also been associated with the development of depression, anxiety, and schizophrenia (Suryadevara et al., 2017). Talk with your health care practitioner about the pros and cons of marijuana use depending on your health needs.

New and Promising Research on Multiple Sclerosis

Recent studies have investigated the virologic origin of MS, as well as how calcium and tryptophan channels may play a role in MS development. As for treatments, new research suggests that thyroid hormones, gene therapy, and estrogen therapy could be good options.

Viral Origins of MS

One hypothesis about MS development is that it is caused by viruses that are written into our DNA and passed down for generations. These are called human endogenous retroviruses (HERVs). And a new study from researchers at the University of Düsseldorf suggests that HERVs may be reactivated by environmental exposures, triggering an immune attack such as demyelination in the case of MS (Gruchot, Kremer, & Küry, 2019). While this research is still preliminary, there is sound epidemiological evidence to back up the link between viral infections and MS development, and new developments in this field will hopefully help us better understand the origins of MS and how we can best treat it.

Tryptophan

Tryptophan is an amino acid that’s known to be in turkey. While the tale about it making you sleepy is probably not true, studies have shown that dietary intake of tryptophan can affect memory and cognition (Lieben et al., 2018; Sambeth et al., 2009). Several studies have connected tryptophan metabolism (in particular, the kynurenine pathway that produces products that are toxic to neurons) and neurodegenerative disorders, such as MS. While this research is still very preliminary, researchers believe that dysregulated tryptophan pathways may be involved with the demyelination that is characteristic of MS (Watzlawik et al., 2016).

In a particularly interesting study published in 2018, researchers at Brigham and Women’s Hospital found that when gut microbes break down tryptophan, particular cells in the nervous system called microglia and astrocytes may be affected—and that this could alter inflammation in the brain (Rothhammer et al., 2018). Much more research in this area is needed to elucidate exactly what’s at work here, though.

Repairing the Myelin Sheath with Thyroid Hormones

To cure MS, scientists will likely need to discover a way to prevent the myelin sheath from being damaged or find a way to regrow the myelin after the damage has already occurred. Thyroid hormones have been shown to regrow myelin, but they come with substantial side effects, so no drug has yet been developed to regrow myelin. But researchers at Oregon Health & Science University may be getting close, according to a study they published in 2019. The researchers treated mice with sobetirome, a synthetic molecule that mimics the thyroid hormone T3, and with an analogue that targets the central nervous system. The mice treated with these drugs had significant remyelination of their nerve fibers and showed an almost complete recovery (Hartley et al., 2019). The next step is for sobetirome to be tested on human populations in clinical trials to see whether the results can be generalized from mice to humans.

Gene Therapy

A study from the University of Florida in 2017 showed that a particular type of gene therapy was able to cure multiple sclerosis in mice. The researchers injected adeno-associated virus, a small, harmless virus, into mice in order to deliver a gene to the liver coding for a myelin sheath protein. In response, the mice’s immune system stopped seeing this protein as something to mount an immune attack against. The mice produced T immune cells that helped counteract the autoimmune process and essentially stopped the body from attacking the myelin sheath. The researchers found that not only did this therapy protect mice from developing MS, but when it was administered to mice who had MS, their disease disappeared (Keeler et al., 2018). Now this therapy needs to stand the test of clinical trials to show that it indeed works when administered to people with MS.

Estrogen Therapy

Several preclinical studies have shown that estrogen can alleviate MS symptoms and inflammation, but it often comes with a wide array of side effects, like increased cancer risk and heart issues. Thanks to a study published in 2019 by researchers at the University of Illinois Urbana-Champaign, these side effects may be avoidable going forward: A new form of the drug chloroindazole acts on specific estrogen receptors without the associated heart and cancer issues. The researchers found that chloroindazole was able to remyelinate destroyed myelin sheaths on nerve fibers and reduce inflammation in the central nervous system of mice with multiple sclerosis (Karim et al., 2019). Results found in mice don’t always generalize to humans, so we’ll wait to see the results from clinical trials.

Clinical Trials for Multiple Sclerosis

Clinical trials are research studies intended to evaluate a medical, surgical, or behavioral intervention. They are done so that researchers can study a particular treatment that may not have a lot of data on its safety or effectiveness yet. If you’re considering signing up for a clinical trial, it’s important to note that if you’re placed in the placebo group, you won’t have access to the treatment being studied. It’s also good to understand the phase of the clinical trial: Phase 1 is the first time most drugs will be used in humans, so it’s about finding a safe dose. If the drug makes it through the initial trial, it can be used in a larger phase 2 trial to see whether it works well. Then it may be compared to a known effective treatment in a phase 3 trial. If the drug is approved by the FDA, it will go on to a phase 4 trial. Phase 3 and phase 4 trials are the most likely to involve the most effective and safest up-and-coming treatments.

In general, clinical trials may yield valuable information; they may provide benefits for some subjects but have undesirable outcomes for others. Speak with your doctor about any clinical trial you are considering.

Ketogenic Diets and Intermittent Fasting

A few preclinical (animal) studies have suggested that fasting for multiple days and ketogenic diets may improve multiple sclerosis symptoms, perhaps by reducing inflammation and stopping autoimmune attacks and demyelination (Choi et al., 2016; Kim et al., 2012). To test these findings in people, Professor Paul Friedemann, MD, and his team at the NeuroCure Clinical Research Center at Charité University in Berlin are recruiting for a clinical trial. They want to determine whether 18 months of these diets can reduce brain lesions in MS patients. One group of patients will stick to a ketogenic diet. Another group will fast for one week every six months. Every day that they are not fully fasting, this group will intermittently fast by not eating for fourteen hours per day. The control group will eat a vegetarian diet. The research group is recruiting adults with MS at their study location in Berlin.

Chemotherapy for Relapses

Tomas Olsson, MD, PhD, a professor of neurology at Karolinska Institute in Sweden, is studying a chemotherapy drug called imatinib (Gleevec) for MS relapses to determine whether it’s better than the current standard of care: steroids, such as methylprednisolone. (A preclinical study in 2014 suggested that imatinib had therapeutic effects on mice with MS.) Participants will receive either 400 milligrams of imatinib twice daily for 14 days or, if they’re in the control group, one gram of methylprednisolone daily for three days. Other chemotherapy agents such as cladribine are also being tested in clinical trials for MS treatment.

Virtual Reality Treadmill Training

Arnon Karni, MD, at the Tel Aviv Sourasky Medical Center is recruiting adults with MS from two study locations in Israel and Illinois to see if virtual reality (VR) treadmill training can improve their walk speed, attention, and cognitive skills. For the six weeks of the study, participants will walk on a treadmill three times a week while wearing a safety harness and VR headset that will simulate obstacles on their path. The subjects in the control group will also receive treadmill training but with no VR for comparison.

Elezanumab

AbbVie, an American pharmaceutical company, is testing a new drug called elezanumab for both RRMS and PPMS in two different phase 2 clinical trials to determine if it improves disease activity. Participants have been recruited from 50 study locations across the United States. Elezanumab is an antibody that acts against a molecule called RGMa, which has been shown to be high in multiple sclerosis patients. This is an issue because RGMa inhibits neural axon growth and myelination and prevents neuronal recovery after inflammation or trauma.

Transcranial Direct Current Stimulation (tDCS)

Leigh Carbet, PhD, a clinical neuropsychologist at NYU Langone Health, is leading a pilot study to determine whether transcranial direct current stimulation (tDCS) can improve fine motor function in people with progressive MS. Previous studies have shown that tDCS may have benefits for people with MS, such as reducing fatigue, but larger studies are needed. In this study, the treatment will be delivered remotely, allowing participants greater flexibility to accessing care. A trained technician will video-call the subjects, instructing them how to set up the device and where to place the electrodes, which will send electrical current through different regions of the brain to excite neurons. Subjects will receive tDCS stimulation 20 times in 20-minute sessions over the course of the study, followed by a grip test assessment, where they will grasp a device that measures their hand function.

Resources

1. • The Family Caregiver Alliance provides education and support resources for caregivers.

2. • The National MS Society offers resources, programs, and services for people with MS.

3. • The Multiple Sclerosis Association of America is a nonprofit that offers a helpline, a mobile app, and resources for people with MS and their loved ones.

4. • Above MS provides resources for living with MS and for finding treatment, and it has created the She Talks MS video series featuring women with MS and neurologists discussing important topics in the field.

5. • MultipleSclerosis.net is an online community of people with MS.

6. • Walk MS is a charity run by the National Multiple Sclerosis Society to raise money for MS research.