Multiple sclerosis, one of the most devastating neurodegenerative diseases, affects some 2.5 million people worldwide and has no known cure.
Researchers have long speculated that Multiple sclerosis is triggered by the body’s own immune system unleashing an uncontrolled attack on myelin sheaths that protect nerve cells (neurons).
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A study published by Israeli scientists in the Journal of the American Chemical Society (JACS) pinpoints a structural instability in the myelin membranes, the “insulating tape” surrounding neurons.
This vulnerability seems to be what gives the immune system access to otherwise protected regions.
“We found that small modifications in the myelin sheaths create structural instabilities that may help the immune system to enter and attack neurons,” said principal investigator Prof. Roy Beck of Tel Aviv University’s School of Physics and Astronomy and Sagol School of Neurosciences.
“Current therapeutic approaches have focused on the autoimmune response without identifying a clear mechanism. Our research suggests a new avenue for multiple sclerosis therapies and diagnostics,” Beck said.
Breaking down the insulation
Axons, which carry electrical impulses in neurons, are surrounded by protective myelin sheaths. In MS, an autoimmune “error” mistakenly identifies these sheaths as hostile foreign entities and breaks them down.
The research, conducted by Rona Shaharabani, a doctoral student in Prof. Beck’s lab, pinpoints the precise alterations to the myelin sheaths that result in structural instabilities, creating “easy access” for autoimmune attacks.
“After years of research, we were amazed to discover that a possible trigger for the outbreak of the disease could be found in the membrane’s physical structure,” said Beck.
Cylindrical instead of flat
He explained that the lipid-and-protein building blocks of the myelin sheaths give the membrane a shape that is critical to their functioning.
“If the basic building blocks are straight, the membrane will be flat, which is the preferred structure for a neuron’s ‘insulating tape,’” said Beck. “However, if they exhibit a more cone-like shape, the membrane will tend to form closed round cylinders. These produce spontaneous holes on the surface of the sheath, rendering it vulnerable to attack.”
For the purpose of the research, the scientists harnessed X-ray light to examine hundreds of membrane model systems that mimicked those of healthy and diseased animal models.
In collaboration with Prof. Ruth Arnon of the Weizmann Institute of Science in Rehovot, co-developer of the leading MS drug Copaxone, and Prof. Yeshayahu Talmon of the Technion-Israel Institute of Technology in Haifa, the team also used electron microscopy to determine the different nanoscopic structures of both natural myelin sheaths and model system membranes.
“The next step is to find a way to reverse the disease progression and find new techniques for early detection,” said Beck.