Autoimmune Versus Oligodendrogliopathy: The Pathogenesis of Multiple Sclerosis
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Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS); it affect millions of patients worldwide and the number of patients is on the rise. Current treatment options are fairly limited and there is a strong unmet need for disease-targeted therapies for MS. The most widely accepted hypothesis for the pathogenesis of MS is that it is a primary autoimmune disease in which myelin-specific T cells play a central role in the progression of demyelination. According to this hypothesis, a powerful immune suppression or a reconstruction of the immune system to abrogate disease-specific leukocytes early in the development of the disease is expected to halt or even reverse the disease, since remyelination is an exceptionally efficient regenerative process in the CNS. However, recent neuropathological studies have provided evidence of primary oligodendrogliopathy as a cause of demyelination, suggesting that immune reactions may be a mere secondary event in the course of MS. On the other hand, some recent clinical trial results of new immune-suppressive treatments showed a nearly complete blockade of relapses and significant, albeit incomplete, neurological improvement. Therefore, which hypothesis—autoimmunity or oligodendrogliopathy—lights the correct path to a “cure” for MS?
KeywordsMultiple sclerosis Pathogenesis Autoimmune Oligodendrogliopathy
Acute disseminating encephalomyelitis
CC chemokine ligand
Central nervous system
Experimental autoimmune encephalomyelitis
Oligodendrocyte precursor cells
Primary progressive multiple sclerosis
Relapsing-remitting multiple sclerosis
Secondary progressive multiple sclerosis
Tumor necrosis factor
Jin Nakahara is supported by the Keio University KANRINMARU Project. This work was supported by Research Grant no. 09-24 from the National Institute of Biomedical Innovation of Japan, by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Keio University Research Grants for Life Science and Medicine.
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