Multiple sclerosis (MS) is a very cruel neurological disease, usually first appearing during the third, fourth or fifth decade of life – and totally unpredictable. The insulating cover – called myelin – of the axons of nerve cells that carry electrical impulses in the brain and spinal cord is attacked by the body’s immune system, which recognizes it as an “intruder.”
The demyelination causes “shorts,” as in an electrical wire without its plastic coating, disrupting the various parts of the nervous system from communicating.
As a result, muscle weakness, paralysis, vision problems, pain, trouble with coordination and difficulty with sensation appear, usually getting worse with each attack.
MS, which affects more than 2.3 million people around the world, appears in two main forms – relapsing-remitting (isolated attacks) and progressive (getting worse over time). Between attacks, the symptoms may go away, but often, permanent neurological problems remain.
The prevalence of MS varies according to gender, genetic background and where the individual lives; usually, the rate is higher in cooler climates and is much more common in women than in men. With more cases the farther one lives from the equator, it has been suggested that being exposed to less sunlight and vitamin D could be a risk factor.
Over the decades, researchers have suggested that a combination of factors to which the individual is exposed, such as a viral infection, and genetic makeup triggers the attacks. There is no known cure for multiple sclerosis, but various treatments – many of them developed by Israeli researchers – have made the disease manageable for many MS suffers.
More than a dozen different treatments, most of them injected, have been approved by the US Food and Drug Administration, including the well-known Copaxone drug developed over decades at the Weizmann Institute of Science in Rehovot, Israel and made by the Teva pharmaceutical company. These drugs can held reduce the frequency of neurological attacks and their severity.
It was first described in 1868 by Jean-Martin Charcot, and its name refers to numerous scars (sclerae, better known as plaques or lesions) that develop on the white matter of the brain and spinal cord. Patients who feel muscle weakness or a feeling of “ants” running up and down their limbs are usually diagnosed with magnetic resonance imaging (MRI) that images the central nervous system and other parts of the body and examination of the cerebrospinal fluid.
Now, researchers at Tel Aviv University have discovered that certain environmental conditions may make the body more vulnerable and trigger structural changes in the myelin sheaths at the onset of MS.
Their study, just published in the journal Proceedings of the [US] National Academy of Sciences (PNAS) demonstrates that myelin sheaths undergo structural transitions triggered by changes in local environmental conditions such as salt concentration (salinity) and temperature.
The research was led by Prof. Roy Beck of TAU’s School of Physics and Astronomy and conducted by Rona Shaharabani, a doctoral student in Beck’s lab, and Maor Ram-On, a doctoral student in the lab of Prof. Ronen Talmon at the Technion-Israel Institute of Technology in Haifa.
Beck previously revealed that changes in the structure of myelin sheaths are a factor in the development of MS. Current treatment approaches have focused on the autoimmune response without identifying the culprit, explained Beck. “We have found that under certain environmental conditions, such as elevated salinity and temperature, myelin sheaths protecting neurons undergo structural changes consistent with diseased myelin structures in MS.”
“In such a normal state, myelin is formed by self-assembly of proteins and fatty acids, which together form a multi-layered envelope like a jellyroll around the nerve fibers. In MS patients, however, the cocoon undergoes a structural change and is like a honeycomb.”
The immune cells can penetrate the myelin and attack it from the inside, and we wanted to see if the structural changes in myelin could be caused by local changes in the physiological environment – that is, the types and concentrations of the salts and the temperature.
A small change in the physiological concentration of each of the salts separately can cause a change in the myelin structure created in the test tube – from a healthy jellyroll to the honeycomb characteristic of MS. It was also found that the structural change was also created at a temperature greater than 42 degrees Celsius
“The myelin sheaths undergo structural transitions at the molecular level when affected by different environmental conditions. These small modifications create structural instabilities that allow the immune system to attack neurons,” added Shaharabani.
The researchers used X-ray scattering and cryogenic transmission electron microscopy (cryo-TEM) to track and measure the myelin sheaths in healthy and diseased animal models. They found that healthy membranes spontaneously morphed into different pathological structures of nanoscale tubes called inverted hexagonal shapes.
“These results highlight that local environmental conditions are critical for myelin function. These conditions should be considered as alternative possibilities for early diagnosis and as a means of avoiding the onset of demyelination,” continued Shaharabani. “Since we believe that these structural modifications result in vulnerability of the myelin membrane to the immune system attacks, it can help explain the causes of MS and, we hope, pave the way for a treatment or a cure.”
As the researchers reached a new biophysical understanding for investigating the breakdown of myelin sheaths, they have started to examine more factors that could induce such structural changes. There are several molecular candidates, including specific proteins and other alterations in the myelin’s fatty acids, that are relevant. This may unravel further insights to fight multiple sclerosis and related disorders, concluded Shaharabani.