This image shows a region of de-myelinated nerve cells (dark patch in the center) surrounded by otherwise healthy cells (green).
Image credit: Maria Traka/University of Chicago
However, it is possible to prevent the trigger with nanoparticles - even after the myelin-producing cells are lost - say the researchers, who are already preparing the nanoparticles for clinical trials.
The study, from the University of Chicago and Northwestern Medicine - also of Chicago, IL - is published in the journal Nature Neuroscience.
The findings are the result of using a new strain of mice for studying multiple sclerosis (MS).
About 2.5 million people around the world have MS, a disease with no clear cause and no known cure, where the immune system abnormally attacks myelin - the protective sheath that insulates nerve fibers and the signals they carry.
Symptoms of MS range from blurred vision and weak limbs to tingling sensations, unsteadiness and fatigue.
In some people with MS, the symptoms gradually get worse with time, while in others, there are periods of relapse interspersed with periods of remission.
Brian Popko is a professor of neurological disorders at Chicago and co-senior author of the new study. He says although their research was conducted in mice, it reveals for the first time a possible mechanism for triggering MS - the death of myelin-producing nerve cells. He adds:
"Protecting these cells in susceptible individuals might help delay or prevent MS."
New mouse model enabled study of myelin-producing cells
For the study, the team bred a new strain of mouse so they could better investigate the causes of MS, and in particular, study oligodendrocytes - cells in the central nervous system that produce myelin.
When they deliberately targeted and killed oligodendrocytes, the team saw how the mice could not walk very well - an MS-like symptom.
Then, after this initial reaction, the mice's central nervous system restored the myelin-producing cells and the animals were able to walk normally again. But after 6 months, the MS-like symptoms came back.
The researchers found that the later onset of MS-like symptoms coincided with increased numbers of T cells in the central nervous system. They also found T cells specifically primed with the myelin antigen oligodendrocyte glycoprotein (MOG) in the mice's lymphatic system.
T cells are a type of white blood cell that helps the immune system identify targets by recognizing unique proteins or antigens on their surfaces.
Events that can cause the death of oligodendrocytes include abnormal development, viruses and toxins, such as from bacteria or environmental pollutants.
Nanoparticles prevented MS-like symptoms in mice
The team believes this is the first evidence that the death of oligodendrocytes can launch an immune system attack on myelin and trigger the inflammation and tissue damage of the central nervous system seen in MS.
They suggest that in humans, the event that triggers the death of oligodendrocytes could happen years before MS starts to develop.
The new strain of mouse that the team used in the study allows the testing of new drugs against progressive MS.
In a second part of the study, the researchers tested nanoparticles devised to make the immune system less responsive to the myelin antigen.
When they administered the nanoparticles to the mice, it prevented the development of the progressive MS-like symptoms.
The nanoparticle technology has been licensed to Cour Pharmaceutical Development Company, who are now developing it for human trials in autoimmune disease.
New perspective on cause of MS
The study offers a new perspective on theories about the cause of MS. Current thinking suggests the trigger for MS is something outside the nervous system that sets off the disease in genetically predisposed individuals. The event somehow causes T cells to see a protein in the myelin sheath as foreign. These primed T cells then trigger the immune attack on myelin.
But the new study offers a different view and suggests it is possible for MS to begin inside the nervous system, as a direct consequence of damage to oligodendrocytes - the cells responsible for the maintenance of the myelin sheath.
If these cells die, then the myelin begins to disintegrate, and when this happens, bits break off and present as antigens, priming T cells to alert the immune system and launch a full-scale attack on anything bearing that hallmark, including healthy and intact myelin.
Prof. Popko concludes:
"It will be exciting to determine the nature of this process in humans - its precise role in MS and whether therapies to prevent it are effective."
Earlier this year, Medical News Today learned of a study by a German team published in the journal Immunity that showed dietary fatty acids may influence flare-ups in MS and other autoimmune diseases.