Scientists say multiple sclerosis is not an autoimmune disease

Scientists suggest that multiple sclerosis, long considered an autoimmune disease, is not really a disease of the immune system. Dr. Angelique Cortels, a forensic anthropologist, and John Jay, a professor at the College of Criminal Justice in New York City, suggest that multiple sclerosis, which is caused by a lipid disorder, is more similar in many ways to coronary atherosclerosis than to other autoimmune diseases.

Cortels believes that viewing MS as a metabolic disorder helps explain many of the mysterious aspects of the disease, including why it affects more women than men and why the incidence has been on the rise around the world. She suggests that this hypothesis could help scientists develop new treatments and, eventually, a cure for the disease.

Today, multiple sclerosis affects at least 1.3 million people worldwide. Its hallmark is systemic inflammation that leads to scarring of tissue called myelin, which insulates the nerve tissue of the brain and spinal cord. Over time, this scarring can lead to serious neurological damage. Scientists have suspected that the immune system is to blame, but no one has been able to fully explain what exactly causes the disease. Genes, diet, pathogens, or vitamin D deficiency may all be linked to multiple sclerosis, but evidence for these risk factors is inconsistent and even contradictory, frustrating scientists in their search for effective treatments.

"Every time a genetic factor has been shown to significantly increase the risk of developing MS in one population, it has been found to be of little significance in another population," says Cortels. "It is also impossible to explain the involvement of pathogens, including Epstein-Barr virus, in the development of the disease, since genetically similar populations with similar pathogens differ dramatically in the rate of disease development. The search for MS triggers in the context of autoimmune disorders has simply not led to general conclusions about the etiology of the disease."

However, by considering multiple sclerosis as a metabolic rather than an autoimmune disease, one can see the common pathogenesis and causes of the development of this disease.

Lipid hypothesis

Cortels believes that the root cause of MS may be transcription factors in the nuclei of cells that control the uptake, breakdown, and production of lipids (fats and other similar compounds) throughout the body. The disruption of these proteins, known as peroxisome proliferator-activated receptors (PPARs), causes a toxic byproduct, LDL cholesterol, to accumulate, forming plaques in the affected tissues. The accumulation of these plaques, in turn, triggers an immune response that ultimately leads to scarring. This is essentially the same mechanism involved in the development of atherosclerosis, in which a lack of PPARs leads to plaque formation, an immune response, and scarring in the coronary arteries.

"When lipid metabolism is disrupted in the arteries, you get atherosclerosis," explains Cortels. "When it happens in the central nervous system, you get multiple sclerosis. But the underlying cause is the same."

A major risk factor for developing lipid homeostasis disorders is high LDL cholesterol. So if PPARs were the basis for the development of MS, it would explain why cases of the disease have been increasing in recent decades. "In general, people around the world consume more sugar and animal fats, which often lead to high LDL cholesterol," Cortels said. "So we would expect to see higher rates of lipid-related diseases - such as heart disease and, in this case, MS. This also explains why statins, which are used to treat high cholesterol, have shown good efficacy in MS."

The lipid hypothesis also sheds light on the link between multiple sclerosis and vitamin D deficiency. Vitamin D helps lower LDL cholesterol levels, and vitamin D deficiency increases the likelihood of developing the disease - especially in the context of a diet high in fat and carbohydrates.

Cortels also explains why multiple sclerosis is more common in women.

"Men and women metabolize fats differently," Cortels said. "In men, PPAR abnormalities are more common in vascular tissue, so they have a higher incidence of atherosclerosis. Because of their reproductive role, women metabolize fats differently. The abnormal lipid metabolism in women is likely influenced by myelin production in the central nervous system. So, multiple sclerosis is more common in women, and atherosclerosis is more common in men."

In addition to high cholesterol, there are other factors that impair PPAR function, including pathogens such as the Epstein-Barr virus, trauma, and certain genetic profiles. In many cases, one of these risk factors is not enough to cause lipid metabolism collapse. But a combination of many factors can lead to lipid metabolism disorder. For example, a genetically weakened PPAR system alone may not cause disease, but when combined with a pathogen or poor diet, it can cause multiple sclerosis. This helps explain why different triggers for multiple sclerosis are important for some people and populations but not for others.

Scientists plan to conduct more research to fully understand the role of PPARs in MS, but Cortels is hopeful that this new understanding of the disease could ultimately lead to new treatments and prevention measures.

"This new hypothesis gives us more hope than ever for a cure for multiple sclerosis," Cortels said.

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