Your Genes and Multiple Sclerosis (MS)

 

By Paul Frysh

Medically Reviewed by Sabrina Felson, MD on April 19, 2022

In basic terms, scientists simply don’t know what causes multiple sclerosis, or MS. Your genes – the genetic material that you inherit from your biological parents – play at least some part. But they are not the sole cause.

In MS, your immune system goes haywire and starts to damage your central nervous system (brain and spinal cord). Scientists are still trying to figure out how this response works and what causes it. Scientists think that for some people, genes may cause your immune system to interact with something in some way to cause the disease.

These may include:

Environment. Environmental factors, like smoking, low levels of vitamin D, and obesity in childhood, have been shown to raise the risk for MS. People who live in certain parts of the world – for instance, those further away from the equator – tend to get MS more often. The reasons for this aren’t yet clear. Some scientists think it involves higher vitamin D levels near the equator.

There are also some theories that exposure to things like chemical solvents and allergens, among other things, contribute to MS risk. But research hasn’t shown this yet.

Infections. Infection with certain germs may raise your risk for MS. Research points in particular to the virus that causes mononucleosis (Epstein-Barr virus). But scientists are also investigating measles, human herpesvirus-6, and others.

Who Gets MS?

One of the reasons scientists assume a role for genes in the development of MS is that some closely related groups get the disease more than others.

To start with, women are twice as likely as men to develop MS. It’s also more commonly diagnosed in white Americans than Black Americans or those of Asian heritage. And MS is rare or doesn’t exist in many Native American societies. This all suggests that genes may also play a role in who gets MS.

In addition, though many groups share some of the same genes or gene mutations that raise MS risk, this is not always the case. For example, in one study, of 73 genes that raised MS risk in white Americans, only eight did the same in Black Americans. Are there other genes that raise the risk of this disease for Black Americans but not for white Americans? What are they, and might they change the approach to treatment?

More research needs to be done on the causes of MS, both in general and in different ethnic groups so that we can understand both the risk factors for MS and the right way to treat it in different people.

 

Can You Inherit MS From Your Parents?

Not really. There is no known gene or set of genes that guarantees that you will get MS if your parents have it. But a family history of MS does raise your risk for the disease.

For example, the rate of MS in the general population is about 1 in 1,000. But if you have a parent with MS, your chances go up to 1 in 50. And if both parents have MS, your risk goes up further to about 1 in 8. Other possible family history situations show that the closer your relationship to someone with MS, the higher your chances of having it:

If a second-degree relative (grandparents, uncles, aunts) or third-degree relative (great grandparents, great uncles and aunts, first cousins) have MS, your risk is about 1 in 100.

If your sibling or non-identical twin has MS, your risk is about 1 in 20.

If your identical twin has MS, your risk is about 1 in 4.

Scientists are especially interested in statistics about twins because identical twins have exactly the same genetic material. So if genes were the sole cause, both should have MS. But most of the time only one twin gets it, which means other things are at work.

Which Genes Raise Your Risk for MS?

Scientists know of more than 200 genes or genetic variations (mutations) that may contribute to MS. A lot of these genes help build and maintain the immune system. Some of them are linked to other diseases that also involve a malfunction of the immune system, such as Crohn’s disease and rheumatoid arthritis.

Others simply increase your chances for developing certain risk factors for MS. For example, lower vitamin D levels raise the risk of MS in some people. Certain gene variations are linked to lower vitamin D levels and thus a higher risk of MS. And genes that raise your risk of having high BMI (a measure of body fat) – another risk factor for MS – also make you more likely to get the disease.

In some cases, there may be particular gene mutations that raise your risk of MS, but in many people, it seems to be that no single gene raises your MS risk, but that it’s the interaction of several of them.

Researchers continue to look for more clues about the relationship between genes and MS.

 

Promising Vaccine for 'Mono' Virus, Cancers, and MS

 

By Dennis Thompson
HealthDay Reporter

THURSDAY, May 5, 2022 (HealthDay News) -- Two experimental vaccines show promise in protecting against infection with the "mono" virus, which also causes cancer and has been implicated as a potential trigger of multiple sclerosis, a new paper reports.

Tested only in animals so far, the vaccines block two pathways by which the Epstein-Barr virus (EBV) takes root inside the body, said senior researcher Dr. Gary Nabel, president and CEO of ModeX Therapeutics, a small biotech startup in Natick, Mass.

Epstein-Barr is tricky to prevent because it takes up residence in two types of cells, Nabel said — B immune cells that produce antibodies, and epithelial cells that line the internal and external surfaces of the body.

These new vaccines are genetically engineered to induce an immune response that would block infection of both cell types, Nabel said.

"That gives us an opportunity to really damp down any foothold the virus may be able to take in establishing itself in the body," Nabel said. "That's why we think that this is a worthwhile approach, because we've essentially isolated two critical entry proteins for the virus, and can block its ability to enter cells and cause infection."

Currently, there's no approved vaccine that protects against Epstein-Barr virus, which has infected more than 95% of adults worldwide, researchers said in background notes.

Epstein-Barr is primarily known as the cause of mononucleosis.

"It infects B cells in the body, your antibody-producing cells, and it causes those cells to proliferate abnormally," Nabel said. "You get a lot of inflammation, and you get a lot of immune dysregulation. And that's why people feel lousy. That's why it takes several months to get over. That's why you get super infection with these sore throats and upper respiratory symptoms, and these systemic symptoms that give rise to infectious mono."

But EBV also was the first human virus associated with cancers, primarily lymphomas and gastric cancers, Nabel said. The virus causes more than 200,000 cases of cancer every year.

More recently, researchers also have learned that a person's risk of multiple sclerosis (MS) skyrockets 32-fold if they've been infected with Epstein-Barr, according to a study published in Science in January.

It's believed that EBV triggers MS in some people by tricking the immune system into attacking the body's own nerve cells, according to another January study published in Nature.

The experimental vaccines work by genetically fusing two different attachment proteins — the keys that allow EBV to enter B cells and epithelial cells — onto a common particle called ferritin, Nabel said.

Ferritin's regular job is to carry iron in the bloodstream, but the genetic engineering gives it an extra purpose, Nabel said.

"It serves as a carrier, where we can essentially decorate the outside of the particle with the viral proteins," Nabel said. The immune system sees the viral infection proteins and mounts a response that theoretically would protect against future infection by the real virus.

The vaccines prompted strong antibody responses in mice, ferrets and monkeys, according to a new report published May 4 in Science Translational Medicine.

The vaccines also appeared to block development of lymphomas in "humanized" mice — rodents grafted with human stem cells.

The researchers hope to start human clinical trials for the vaccines within a year, Nabel said. However, it's important to note that results obtained from animal studies aren't always replicated in humans.

Effective EBV vaccines will be the key to ultimately proving the link between the virus and MS, said Bruce Bebo, executive vice president of research programs for the National MS Society.

"In order to prove causation, there's one experiment left to do. That experiment is to have a vaccine and deploy the vaccine, and then observe over a period of time whether it can prevent MS," Bebo said. "We have everything we need to know now to justify an investment in that type of experiment, once we have a safe and effective vaccine."

This study was funded by Sanofi, one of the pharmaceutical companies developing the vaccine.

More information

The U.S. National Institutes of Health has more about Epstein-Barr virus and multiple sclerosis.

SOURCES: Gary Nabel, MD, PhD, president and CEO, ModeX Therapeutics, Natick, Mass.; Bruce Bebo, PhD, executive vice president of research programs, National MS Society; Science Translational Medicine, May 4, 2022

 

Are Off-Label Drugs Safe for Treating MS?

 

When your doctor suggests a drug to treat your multiple sclerosis (MS), your first move may be to search the internet to learn more about it. You may be surprised to find that the medicine is "off-label," which means it isn't approved to treat MS.

Is that a good idea, you wonder? The answer: It can be. A lot depends on how the medicine works and whether the benefits outweigh the risks.

Over the years, doctors have prescribed everything from cancer drugs to acne medicine to help with MS. So you have a lot of options.

When Would I Try One?

Your doctor might suggest going off-label if approved drugs aren't safe for you. You might have allergies to some medicines or find that side effects hit you too hard. Or you might have another condition that means you need to avoid certain medications.

In other cases, you might have tried the standard medications and found they didn't get the job done.

What Are the Risks?

The FDA approves drugs to treat specific conditions. Then, doctors get guidelines on when to use them, how much to give, and what side effects to look for.

When you go off-label, you're in a gray area. A cancer drug doesn't get tested in someone with MS to see if it acts any differently or to check which dose works best. So there's some extra risk there.

That said, many off-label meds for MS often have at least some research behind them. When studies show off-label drugs work for MS, they tend to have fewer risks.

Your best bet is to talk it through carefully with your doctor. Ask questions like:

• What studies show the drug works for MS?
• What are the side effects and risks for someone with MS?
• Are there clinical trials I could join?

How Long Can I Use Them?

It depends on a lot of things like the dose, other conditions you have, and other medicines you take. For some drugs, there may not be enough research to know. New studies come out all the time, so check with your doctor.

Which Off-Label Drugs Treat MS?

You have a lot of choices. Some medicines your doctor may suggest are:

Amantadine (Osmolex ER). It's used to treat the flu and Parkinson's disease, but it may help with fatigue from MS. It generally has few side effects and seems safe.

Azathioprine (Imuran). Doctors have prescribed this drug to treat MS for over 40 years. It can cut the number of relapses you get and keep your MS from getting worse. If you use it for more than 10 years or take more than 600 grams over your lifetime, it may raise your risk of cancer.

Cyclophosphamide.Doctors sometimes recommend it for progressive forms of MS, but results have been mixed. It may slow down your disease and help with symptoms, but it can also come with side effects like nausea and vomiting that can be tough for some people.

Duloxetine (Cymbalta, Irenka). Your doctor may suggest it to treat pain and depression from MS. It seems generally safe and without too many side effects.

Methotrexate. It can slow down progressive forms of MS and may put off problems in your shoulders, arms, and hands. One study showed that it was safe to use for at least 3 to 6 years.

Minocycline. An antibiotic originally used for acne, this drug's been around for 50 years. It looks to be helpful in slowing down relapsing-remitting MS in people who recently had their first symptoms.

Mycophenolate mofetil (CellCept). This drug may cut down on your relapses and slow down the disease. It may raise your chances of getting cancer or an infection. More research is needed to see if it's safe to take long term.

Pregabalin (Lyrica). This is another option for treating pain from MS. It looks to be safe with few side effects.

---

Rituximab (Rituxan). It can slow down relapsing-remitting MS and cut back on relapses. For most people, it doesn't seem to cause any major issues.

Simvastatin (Zocor). It's typically used for high cholesterol, but it shows promise in slowing brain shrinkage from secondary progressive MS. And it's considered safe with few side effects.

 https://www.webmd.com/multiple-sclerosis/off-label-drugs-treat-multiple-sclerosis?ecd=wnl_mls_050622&ctr=wnl-mls-050622_lead_cta&mb=q80%2F%40kIeuyYKtyaYzOxdbc6RVoMqf%400VkpmvpK5yEEQ%3D

 

Why Multiple Sclerosis Affects More Women Than Men

 

By Rachel Reiff Ellis 

 

Women with MS outnumber men with the condition by nearly 4 to 1. And this gender gap has only widened in the last 50 years. Experts don’t have a clear explanation for the cause of MS in anyone, much less in women specifically. But they have a few theories that might explain the sex differences in MS rates.

Immune System Differences

DID YOU KNOW?

Women with MS outnumber men with the condition by nearly 4 to 1.

Share on Twitter

Women’s immune systems work differently from men’s. Specifically, women are more likely to develop autoimmune diseases. In fact, nearly 7 in 10 people with autoimmune diseases are women.

The difference might lie in an immune system protein called interleukin-33 (IL-33). It helps cells within the immune system communicate with each other. This is how they work together to fight off infection.

Current research explores what role IL-33 might play in immune system responses in men and women.

Early studies show that men make more IL-33 than women when they face infections. This may explain why women are more likely to have an autoimmune response than men are.

Nervous System Differences

Men tend to get more nerve damage with MS than women do. Researchers think this may have to do with estrogen levels. Women’s bodies produce more estrogen than men’s. This leads researchers to ask whether estrogen may protect nerves in some way.

 

 

Hormone Changes

One reason that more women develop MS than men could have to do with reproductive hormones. Before puberty hits, boys and girls tend to get MS at about the same rate. But as boys and girls move into adolescence and adulthood, when the male and female bodies make different hormones, women begin to get MS at higher rates than men. This difference pushes researchers to consider a possible link between male and female sex hormones and MS. 

Genetics

Mutations in certain genes called MHC genes may raise the risk for MS. Some research shows that women with MS are more likely to have relevant changes in these genes than men. Daughters are also more likely than sons to inherit those gene changes from their mothers.

But a gene alone likely doesn’t cause MS. Researchers think that other factors in your life, such as diet, smoking, stress, and the amount of sunlight you get, influence how these MS-related genes behave.

Body Fat

Obesity, especially in the form of belly fat, can cause inflammation in your body. And inflammation plays a role in MS. Obesity-related inflammation may arise more often in women than in men. That’s because women tend to carry more body fat than men do, and they are more likely to become obese. Scientists think the rising numbers of women with MS may relate to this higher percentage of body fat.

 https://www.webmd.com/multiple-sclerosis/ms-affects-women-more-than-men?ecd=wnl_mls_040122&ctr=wnl-mls-040122_supportTop_cta_2&mb=q80%2F%40kIeuyYKtyaYzOxdbc6RVoMqf%400VkpmvpK5yEEQ%3D

We Have Come So Far

When Sylvia Lawry started the MS movement in 1946 with the founding of the National MS Society, research into multiple sclerosis was almost non-existent. The disease took years to diagnose, and there were no therapies proven to slow the course of MS.

Things have changed. Decades of research into MS and the basic workings of the immune and nervous systems have built a critical platform of knowledge now serving as a springboard for progress. The Society’s $1.06 billion research investment has fueled many of these advances, and today’s picture looks different for many:

• There are therapies specifically approved for treating and managing MS, and more potential MS therapies in development today than at any other time in history.

• MS is more quickly diagnosed, enabling early and sustained therapy to slow disease activity

• There is much greater awareness of the many symptoms of MS and ways to address them to improve quality of life

• Scientists are making breakthroughs in identifying risk factors that can increase a person’s susceptibility to MS, which will help lead to ways to prevent the disease.

We have made progress but more must be done for those living with forms of progressive MS for which there are limited treatment options.  The hope – and potential - for new, more effective treatments for MS has never been greater. We are part of a global movement of millions of people working toward a world free of MS.

Critical Milestones

1981 - First MRI pictures of a brain affected by MS are produced, revolutionizing MS diagnosis
1984 - First modern documentation of cognitive problems in MS
1988 - First demonstration, using MRI, of significant lesion activity in MS, even when the disease seems quiet
1993 - First disease-modifying therapy for relapsing MS approved
1996 - First proof that aerobic exercise improves physical and psychological well-being in MS
1999 - Society grantees first to isolate immature cells in the adult brain capable of developing into replacements for myelin-making cells destroyed by MS
2003 - Italian researchers transplant cells to enhance nerve tissue repair in mice with MS
2004 - Pivotal study by Society Fellow shows that African-Americans tend to have a more aggressive course of MS than Caucasians
2005, 2010, 2018 - “McDonald Criteria” for diagnosing MS updated by Society Task Force, speeding time to diagnosis for many
2007 - With support from Society to International MS Genetics Consortium, two genes are confirmed to be linked to MS risk; many more uncovered since
2007 - First large-scale trial of sex hormone estriol gets underway in women with MS, a result of the Society’s targeting of gender differences
2010 - First oral disease-modifying therapy approved for relapsing MS
2012 - Launch of Progressive MS Alliance to speed the development of therapies
2013 - Studies hint that exercise and rehabilitation can improve many functions and even help rewire the brain
2014 - First large, phase 2 clinical trials of myelin repair strategy for MS are launched
2015 - A phase 2 clinical trial co-funded by the Society suggests a pill used to treat epilepsy (phenytoin) has the potential to slow the accumulation of disability in people with MS
2015 - Results of phase 2 trial of anti-LINGO suggests it has potential as myelin repair strategy 
2015 - Society co-hosts international conference on cell-based therapies to forge next steps for cell therapy in MS
2015 - Society funding helps launch MS Microbiome Consortium to promote research on role of gut bacteria in MS progression and treatment
2015-16 - Two large-scale clinical trials break through long-standing barrier by showing benefit in primary progressive and secondary progressive MS
2016 - Positive results announces from two studies of bone marrow-derived stem cells (HSCT) in people with aggressive, relapsing MS; more research focuses on who might benefit and how to reduce risks
2016 - Society-funded International Consortium of MS Genetics identifies 200 genetic variations linked to MS, offering new leads to how genes and other factors that make people susceptible to developing MS
2016 - Society launches two new studies testing the ability of dietary approaches to treat MS symptoms and improve quality of life  
2016-17 - International Progressive MS Alliance awards three large-scale Collaborative Network Awards to promote solutions for people with progressive MS
2017 - FDA approves Ocrevus (ocrelizumab) as first disease-modifying therapy for primary progressive MS, and also as a therapy for relapsing MS
2017 - International team co-sponsored by the Society revised MS diagnostic criteria to speed diagnostic process and reduce incidence of misdiagnosis
2018 - FDA approves expansion of the use of Gilenya to include children and adolescents 10 years of age or older with relapsing MS, the first therapy specifically approved to treat pediatric MS
2018 - A Phase 2 trial showed that ibudilast could reduce brain atrophy in progressive MS. The trial was funded collaboratively by the National MS Society, the NINDS, its NeuroNext trials network, with support by MediciNova, the supplier of ibudilast 
2018-19 - Results announced from several studies of bone marrow-derived stem cells in people with aggressive, relapsing MS. More research is focused on who might benefit and how to reduce risks
2019 - Study sponsored by the National MS Society conducted by leading experts estimates that nearly 1 million adults are living with MS in the United States. This is more than twice the previously reported number
2019 - FDA approves oral Mavenclad (cladribine) for adults with relapsing forms of MS, and also approves oral Mayzent (siponimod) for adults with clinically isolated syndrome (an initial neurological episode) and relapsing forms of MS
2019 - FDA approved Vumerity™ (diroximel fumarate, Biogen and Alkermes plc) for relapsing MS
2020 - National MS Society releases recommendations for aHSCT-bone marrow transplant for MS
2020 - FDA approves generic form of Tecfidera for relapsing MS
2020 - FDA approves Kesimpta® (ofatumumab) for relapsing MS
2020 - Society-supported Wellness Research Group publishes exercise and physical activity recommendations for ALL people with MS
2020 -  National MS Society, Consortium of MS Centers, and others establish the North American MS COVID-19 Clinical Database
2020 - FDA approves Oral Bafiertam™ (Monomethyl Fumarate) for relapsing MS
2020 - FDA approves Oral Zeposia® (Ozanimod) for relapsing MS

Download a Timeline of MS Research Progress (.pdf).

 

Can Vitamin D Help MS?

 By Stephanie Watson

You might have heard that vitamin D helps to lower the risk for multiple sclerosis (MS). Or that it helps lessen symptoms in people who already have the disease. Evidence suggests that getting enough of this vitamin might protect against MS by holding back your immune system from attacking your own nerve cells.

But the link between vitamin D and MS isn't proven yet.

The MS-Vitamin D Link

This fat-soluble vitamin acts like a hormone in your body. Vitamin D also helps your immune system work better and to tamp down inflammation.

Those protective actions are important in autoimmune diseases like MS where your body turns against itself. In MS, cells of your immune system attack the coating around nerve fibers, called myelin, and leads to such hallmark symptoms as numbness, weakness, and blurry vision.

Research finds that vitamin D might help repair myelin and guards your nerves from damage.

Can Vitamin D Prevent or Slow MS?

Researchers aren’t sure if vitamin D can keep you from getting MS in the first place. Your body makes most of the vitamin D it needs from sunlight on your skin. People in northern climates like Scotland and Scandinavia are more likely to have MS compared with those who live in much sunnier climates. Studies show that people who get more sunlight and more vitamin D in their diets have a lower risk for MS overall.

There's some evidence that vitamin D might slow MS and make the disease less severe. Studies have found a link between higher vitamin D levels in the blood and less active disease, fewer lesions in their brain and spinal cord, and fewer relapses of symptoms.

In other studies, people with MS who had higher vitamin D levels had less severe disease and disability.

Do I Need More Vitamin D?

It's common for people with MS to be low on this vitamin. It may be hard for you to get outside to get sun often enough. Low vitamin D can also be a side effect of corticosteroids and other MS medications.

Your doctor can run a blood test to check your vitamin D level. You might be able to make up the difference by eating more fatty fish, eggs, and other foods that are high in vitamin D. Or, your doctor might suggest you take a supplement.

It's not clear whether taking a daily vitamin D supplement protects people from getting MS, or slows the disease in those who already have it. Studies suggest it might help, but this hasn't been proven. But since supplements are usually safe to take, it may not hurt to try them.

What Dosage Is Best?

Experts can’t say how much vitamin D is needed to prevent or slow MS. Different medical groups disagree on the ideal amount.

Official recommendations for adults is 400 to 600 international units (IUs) of vitamin D daily.

Ask your doctor what’s right for you. Be careful not to overdo it. Vitamin D helps your body absorb calcium, and you might end up with too much of that mineral. High calcium levels can weaken bones, damage the heart, and increase the risk for kidney stones.

If you already have MS, your doctor can check whether your vitamin D levels are too low. If so, it might make sense for you to take a supplement.