Multiple sclerosis: a slow harakiri of the organism

In this post I want to tell you about the most common non-traumatic disabling disease among young adults: multiple sclerosis.

 

Let’s see first, what is multiple sclerosis?

As usual, here comes a little background. Imagine water pipes of your house. What happens if they get damaged and some cracks appear here and there? Most likely water will flow with much less power out from the sink, proportionally to the amount of damage. Something similar happens with multiple sclerosis. We are talking about a neurodegenerative disease, meaning that it affects neurons in brain and spinal cord. These cells are very peculiar in shape, because they have a cell body from which a single long arm, called axon, develops. Axons can reach even 1 meter of length, which is approximately 10000 times the diameter of the cell body. Along the axon, the neural impulse is transmitted, and it can travel really fast: if you close your eyes and you wave your arm, you feel in real time the changing of the position, because this signal travels to 119 meters per second (m/s) (approximately 390 feet/s). When we touch an object, the impulse travels at 76 m/s (250 feet/s), while the signal transmitted among neurons when we think, travels at 20-30 m/s (65-100 feet/s). The only “slow” signal comes from pain, travelling at 61 centimeters/s (2 feet/s). These high speeds are allowed by myelin, which is an insulating material covering axons. Myelin has the same function as a proper pipe in which water flows, by preventing the signal to be dispersed during the journey. I had to make this introduction to explain what multiple sclerosis is: a disease characterized by damage of the myelin sheath. This results in the problematic transmission of stimuli, hampering the communication within the nervous system. Mental and physical symptoms of multiple sclerosis are the direct consequence of this, and include problems with sight and/or coordination of movements, muscle weakness, troubles with sensation, fatigue, and unstable mood. Depending if symptoms are constant or appear with attacks, multiple sclerosis is called “progressive” or “relapsing”, respectively.

How does the myelin sheath get damaged? Multiple sclerosis is a neurodegenerative autoimmune disease. This means that the immune system of the individual attacks the myelin sheath, destroying it. It doesn’t make sense, right? No one likes to hit with a screwdriver water pipes of his own flat (unless (s)he wants to try to cultivate rice on the kitchen floor). But unfortunately that is it. The cause that activates the immune system against the own neural system is still unknown, but there is a list of genetic and environmental factors that provides some hints.

 

Let’s see them.

In a review published in 2014, Paul Browne and colleagues revealed the prevalence of multiple sclerosis (MS) around the world (basically the amount of people affected by the disease), and you can see the result in the map below.

Prevalence map p8

As you can see, developed and developing countries have higher susceptibility to multiple sclerosis. An interesting finding comes from migration studies: adult migrants moving from low-risk to high-risk countries (i.e.: to Europe) have low risk to develop the disease, but their children, if born in the high-risk country, are at high risk.

The main environmental factors involved in multiple sclerosis are Epstein-Barr virus infection, sunshine exposure (ultraviolet B light), smoking and vitamin D. Evidences indicate that exposure to Epstein-Barr virus (i.e.: infectious mononucleosis) doubles the risk of getting multiple sclerosis. The prevalence of the disease increases with the latitude (with Norway and USA being exceptions), because lower exposure to sunlight (which occurs at a higher latitude) reduces the cutaneous vitamin D production, and this reduction has been implicated in multiple sclerosis susceptibility. The way smoking has been implicated as risk factor for the disease is very interesting. Currently women are more susceptible than men (now the ratio is 3:1), but this has not been always the case. Smoking increases susceptibility by approximately 50%, and can explain up to 40% of the increased incidence in women. Before the Second World War, the ratio was similar between the two sexes. So, what happened afterwards? Simply, women started smoking. Graphs indicating the amount of females smoking and the prevalence of multiple sclerosis in women correlate very well.

From a genetic point of view, multiple sclerosis is a complex disease, because it is not associated to a single gene, but several genes are involved in mildly increasing its susceptibility. I will not spend too much time on this, because the field is really complicated and details unnecessary to know in a brief overview like this one. If you read my post in which I wrote about DNA variations with the QR code example (this one), you may recall that often a mutation in the DNA has a consequence that doesn’t necessarily cause a tumor or another genetic disease, but just predispose to a certain extent to a disease. Multiple sclerosis does not make exception, in fact there is a list of approximately 150 variations associated with it. This means that for each of these 150 modules, one of the four colors is associated with multiple sclerosis susceptibility and if the DNA of a person contains at least one of these susceptibility combinations (color + position), this person has a higher risk to develop the disease compared to someone who doesn’t have any of those.

 

Which treatments are available to cure multiple sclerosis?

Unfortunately this disease is not curable yet, but research made several advancements to improve the course of the disease. Therapies are classified depending on their specificity: some are specific for multiple sclerosis, others are specific for the symptoms (which are shared with other neurodegenerative diseases). The first category includes therapies that target the immune system (immunosuppressant or immunomodulatory) to inhibit the inflammatory action against myelin.

So far there is only a list of factors implicated in multiple sclerosis development. When the mechanism that is the direct responsible of the disease will be discovered, it will become a lot easier to develop a targeted therapy. It is easier to fight an enemy, if you know it.

 

References

Dobson R, Giovannoni G. Multiple sclerosis – a review. European Journal of Neurology 2019, 26: 27–40.

Browne P, Chandraratna D, Angood C, et al. Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity. Neurology 2014; 83: 1022–1024.

Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother 2013; 13: 3–9.

Kurtzke JF. Epidemiology in multiple sclerosis: a pilgrim’s progress. Brain 2013; 136: 2904–2917.

Handel AE, Williamson AJ, Disanto G, Handunnetthi L, Giovannoni G, Ramagopalan SV. An updated meta‐analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One2010; 5: e12496.

Koch‐Henriksen N, Sørensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 2010; 9: 520–532.

Sintzel MB, Rametta M, Reder AT. Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther 2018; 7: 59–85.

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