Multiple sclerosis: can we turn on the right genes?

It starts subtly – most often as a strange tingling, stiffness or loss of sensation in the limbs. Many people don’t even pay attention to it. But this is how a very insidious disease that can turn a person’s life completely upside down manifests itself: multiple sclerosis. The key to its origin and perhaps even its cure, or at least to slowing down its progression, lies in so-called epigenetic processes.

Multiple sclerosis (MS) is a disease of autoimmune nature, in which there is degeneration of nerve cells, and therefore a disruption of the exchange of information between the brain and the rest of the body.

A characteristic feature of MS is demyelination. In this process, there is a significant loss of myelin, which is a structure that encases the nerve fibers and allows proper conduction of nerve signals. If it is disrupted or even completely disappears, the conduction of nerve impulses gradually slows down, up to its complete impossibility.

At the same time, the destruction of axons (long spurs of nerve cells) occurs and the barrier between the bloodstream and the brain is disrupted, which promotes the development of inflammatory processes in the brain.

How does the disease manifest itself?

There can be many symptoms of MS:

• A very typical initial manifestation is tingling, weakness and reduced sensitivity of the limbs, which eventually develops into coordination disorders. Muscle cramps, tremors, difficulty walking, balance problems or stiffness are also common.
• Visual disturbances, especially blurred or double vision, are also a common symptom.
• Skin symptoms such as burning, itching or pain also occur.
• Unfortunately, the disease also affects cognitive abilities. Memory impairment, impaired attention and impaired judgment are common.
• Sexual dysfunction, digestive disorders, incontinence and mood disorders such as depression are also common.
• At an advanced stage, paralysis or dementia may develop.

The first manifestations most often occur between the ages of 20 and 40, and women are affected significantly more often than men.

Most cases of MS (more than 80%) are characterised by alternating periods of remission, when symptoms temporarily disappear, and relapses, when the disease flares up again. Remissions can last for many years.

What role does heredity play?

The exact reason why RS is being created has not yet been fully revealed. However, according to current knowledge, it is a combination of genetic and epigenetic influences. Epigenetic influences are a complex of biochemical reactions that affect the activity of individual genes in our DNA (they can even switch them off or on again) and whose course is strongly dependent on our lifestyle and environment. Infection with certain viruses, such as the herpes virus or the Epstein-Barr virus (EB virus), which also has epigenetic effects, may also play a role.

Heredity is involved to some extent in the development of MS. This is demonstrated by studies on twins, where the rate of concordance in the incidence of the disease was observed in 30% of cases in monozygotic twins, while in only 5% of cases in dizygotic twins. HLA genes on chromosome 6p21.3 are likely to play a major role.

Epigenetics in the lead role

In addition, however, epigenetic changes have been observed in abundance in the patients – in particular, different patterns in several key epigenetic reactions, i.e. in gene methylation, acetylation and citrullination. Different levels of several microRNAs, in particular miR-155 and miR-326, have also been detected.

Inflammatory processes also play an important role in the development of MS. Patients have increased levels of cytokines that promote inflammation (in particular interleukins IL-1, IL-4 and IL-6 and TNFα) and decreased levels of anti-inflammatory cytokines (e.g. IL-10).

Epigenetic changes have been observed in MS patients’ brains as well as in their blood. The changes in the blood are particularly interesting as they could become the basis for non-invasive diagnostics. Here, differences have been found in all the basic epigenetic reactions, especially in gene methylation and also in microRNAs (small, non-coding stretches of RNA that can completely block gene “reading” processes). These have been repeatedly shown in recent years to be an important factor in the development of neurodegenerative and autoimmune diseases.

As far as changes in the brain area are concerned, a reaction called histone acetylation plays a very important role there. When oligodendrocytes, the cells that produce myelin, are in a progenitor state (a state similar to stem cells), there is a high level of histone acetylation in their DNA. As they develop, deacetylation must occur in order for them to function properly. And it is in the brains of patients with chronic MS that an increased rate of histone acetylation has been observed.

However, differences in microRNAs (which have been linked to MS progression) and gene methylation have also been observed in the brain.

Epigenetic changes have also been confirmed in relation to some of the specific problems that accompany MS. For example, people with the disease often suffer from memory problems caused by demyelination in the hippocampus, the part of the brain responsible for memory. Research has confirmed that DNA in the hippocampus is excessively methylated and that the balance of the relevant enzymes is disturbed – specifically, there is an excess of DNA methyltransferase, which is required for the methylation process, and a deficiency of enzymes involved in the opposite process, i.e. demethylation.

A bet on nutrition

Although experts have high hopes for the possibility of using targeted drugs based on epigenetic reactions, their development is still a long way off. On the other hand, it is true that our lifestyle and environment, especially our nutrition, level of physical activity, stress, smoking and toxins from our diet and environment, have a major influence on the course of epigenetic reactions in our body. Therefore, lifestyle modifications can significantly influence both the risk of MS and the course of the disease. In fact, its symptoms often vary according to the season, suggesting that these factors may act as a trigger.

Nutrition is a very important factor. According to research, people who eat a healthy diet not only reduce their risk of developing the disease, but also suffer fewer severe symptoms when they do.

And which specific factors should be focused on?

Vitamin D

The role of this vitamin is one of the best described influences involved in the development of MS. It is a vitamin with extensive epigenetic effects, affecting the activity of several genes involved in autoimmunity. In addition, the VDR receptor, which is located on the cell nucleus and to which vitamin D binds in cells, directly influences the activity of genes involved in MS.

Folic acid

This member of the B vitamin family also has epigenetic effects (it is a methyl donor for methylation reactions). At the same time, it helps regulate the body’s levels of homocysteine, a metabolic product whose high levels are involved in neurodegeneration.

Limiting carbohydrate consumption

So-called ketogenic diets, which are characterized by a significant reduction in carbohydrate consumption, have a proven neuroprotective effect – they help protect nerve cells from the effects of free radicals and reduce their apoptosis (programmed cell death). Although a direct effect of sugar restriction on MS has not yet been demonstrated, it can be assumed, given its positive effects in other neurodegenerative diseases. In addition, a diet with excess carbohydrates is thought to promote inflammatory processes in the body.

Diet rich in omega-3

Omega-3 unsaturated fatty acids have epigenetic effects and are anti-inflammatory, probably because they promote macrophage autophagy (macrophages are immune cells involved in inflammatory processes and autophagy is a process in which cells “eat” themselves).

In addition, omega-3s are also a building block of cell membranes, and their concentration is highest in brain tissue. In addition, research has shown that they can restore the function of damaged oligodendrocytes and promote myelination of neurons.

Therefore, it is important to consume plenty of natural sources of these nutrients, especially fatty fish, nuts, seeds and some vegetable oils (especially hemp and flaxseed), for the prevention and treatment of MS.

Consumption of vegetables containing sulforaphane

Sulforaphanes are organic sulphur compounds with epigenetic effects. They have anti-inflammatory and antioxidant effects and reduce the rate of demyelination and autoimmune responses. They are particularly abundant in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage and cauliflower.

Smoking

Smoking is considered a significant risk factor for MS, mainly due to its negative effect on the rate of gene methylation in the body and the increase in oxidative stress.

Obesity

Obesity is also likely to be a risk factor for MS, especially during childhood and adolescence.

Gut microbiome

An understudied factor, which also plays a role in the development of MS, is the state of the gut microbiome. It is therefore worth focusing on consuming foods containing probiotics and prebiotics.

Motion

Physical activity is an important epigenetic factor. If the patient’s condition permits, he or she should engage in it regularly. Aerobic activities of rather moderate intensity are appropriate.

Dietary supplements

The use of dietary supplements with epigenetic effects can also play a very positive role – these are usually extracts containing nutrients that occur naturally in the human diet, but here they are in a much more concentrated form.

Vitamin D3

The essential role of vitamin D in the onset and development of MS has been described many times. And since deficiency of this vitamin is very common in our latitudes, it is advisable to supplement it at least in winter. The animal form known as vitamin D3 is preferable.

Omega-3

Omega-3 unsaturated fatty acids are essential for MS patients. Since our diet does not contain enough of them in most cases, and we usually consume a completely inappropriate ratio of omega-3 and omega-6 unsaturated fatty acids, which promotes the course of inflammatory processes, it is advisable to take omega-3 in the form of dietary supplements.

EGCG

Epigallocatechin gallate has positive effects in most autoimmune diseases. In addition, in studies on mice, a positive effect on oligodendrocytes, i.e. myelin-producing cells, has been demonstrated.

Curcumin

Similarly, curcumin, a dye found in turmeric root, may be very beneficial in MS according to studies – like EGCG, it has been used successfully in a number of autoimmune diseases. In fact, it has strong anti-inflammatory and antioxidant effects, influences the production of cell cycle regulatory proteins, enzymes, cytokines and transcription factors, and has a significant neuroprotective effect. For better absorption, curcumin should be taken together with piperine.

Ginger

Ginger root, especially its active ingredient 6-shogaol, has significant immunomodulatory and anti-inflammatory effects and is a powerful antioxidant. Its combination with curcumin is also very effective.

On the contrary, the use of resveratrol from red wine is inappropriate. Although this substance is successfully used in some neurodegenerative diseases, it is not only ineffective in MS, but may even promote demyelination.