Protection for myelin
Molecular "imitators" of thyroid hormones – potential drugs for multiple sclerosis
Today, almost three million people in the world suffer from multiple sclerosis – one of the most common neurological disorders and a frequent cause of disability in young people. There is no effective treatment for this pathology, but recently American scientists have created a compound that helps reduce the severity of the disease in laboratory animals.
Article by Chaudhary et al. Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE is published in the Journal of Neuroimmunology.
Multiple sclerosis, a chronic autoimmune disease of the nervous system, is based on damage to the myelin sheaths of nerve fibers through which a nerve impulse passes from cell to cell.
Nerve fibers are axons – long processes of neurons. Like electrical wires, axons are covered with a kind of insulation, the role of which is played by the myelin sheath, which provides a high (up to 80-120 m / s) signal transmission rate.
At the same time, myelin itself is not a substance at all, but a set of many layers of the cell membrane "wound" on the axon. It is formed by flat outgrowths of "service" cells of the nervous system, in which there is practically no cytoplasm. In multiple sclerosis, due to the destruction of myelin, the conduction of nerve impulses is disrupted, and various neurological symptoms develop.
The shell of axons of neurons of the central nervous system is formed by auxiliary cells of oligodendrocytes. It is known that the differentiation of these cells and the process of myelination of nerve fibers is regulated by thyroid hormones. Studies on mice serving as an animal model of multiple sclerosis have shown that thyroid hormones reduce inflammation, prevent the destruction of myelin and damage axons. However, they cannot be directly used for the treatment of multiple sclerosis in humans due to toxic effects.
The compound sobetir is a mimetic (a substance that causes a similar effect in the body) of thyroid hormones and is able to bind to one of their cellular receptors, while it is practically non-toxic. Moreover, its predecessor was synthesized – the compound Sob-AM2, capable of penetrating through the blood-brain barrier directly into the brain. Its use further reduces the risk of side effects on the body.
Previously, in mouse models of demyelination, it has already been shown that sobetir and Sob-AM2 stimulate the restoration of myelin. And now researchers have evaluated their effect on the course of experimental autoimmune encephalomyelitis in mice serving as a standard model of multiple sclerosis.
Animals were injected with sobetir, Sob-AM2 or triiodothyronine (one of the two most active thyroid hormones), starting from the 7th day after the onset of the disease, but before the onset of symptoms. It turned out that all these compounds, protecting oligodendrocytes from death, significantly reduced myelin degradation and axon damage. The greatest effect on the severity of the disease was the introduction of Sob-AM2; the second most effective was sobetir.
The mechanisms of action of thyroid hormones and their mimetics on the development of multiple sclerosis are obviously mediated by the interaction of these compounds with the immune system and are completely incomprehensible. Probably, one of these mechanisms is to reduce the activity of brain macrophage cells involved in the destruction of myelin in multiple sclerosis.
In any case, if the effectiveness of sobetirom, especially Sob-AM2, is confirmed in human trials, a new drug can be introduced into clinical practice. First of all, it will be shown to patients with the initial manifestations of multiple sclerosis.
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