Multiple Sclerosis is an autoimmune disease that attacks and destroys a structure known as the "myelin sheath", whose integrity is indispensable for the brain and spinal cord to function properly.
Current treatment of Multiple Sclerosis is based on modulating the activity of the immune system or preventing its cells from accessing the central nervous system and damaging it. These therapies are effective in the early phases of the disease, but they do not prevent its advance and the progressive functional deterioration.
During the progressive phase of the disease it is the microglial cells in the brain that are the main cause of the chronic inflammation responsible for the neurological deterioration. These microglial cells are the brain's sentries and react when faced with any damage or infection in it. This reaction, which is in principle beneficial, becomes harmful when it is prolonged over time, leading to chronic inflammation, and aggravates the disease and encourages its progression.
In the work just published it was possible to identify a receptor known as P2X4 present in the microglial cells that increases their anti-inflammatory potential in order to reduce the damage in Multiple Sclerosis and, above all, encourage the body's own repair responses.
This experimental development was conducted using animal models of this disease, thanks to which it was possible to discover that the drugs that activate this receptor improve the symptoms during the chronic phase of the disease when furthering the repair of the nervous tissue.
Authors show that blocking P2X4R signaling exacerbated clinical signs in the experimental autoimmune encephalomyelitis (EAE) model and also favored microglia activation to a pro-inflammatory phenotype and inhibited myelin phagocytosis. Moreover, P2X4R blockade in microglia halted oligodendrocyte differentiation in vitro and remyelination after lysolecithin-induced demyelination.
Conversely, potentiation of P2X4R signaling by the allosteric modulator ivermectin (IVM) favored a switch in microglia to an anti-inflammatory phenotype, potentiated myelin phagocytosis, promoted the remyelination response, and ameliorated clinical signs of EAE.
The senior author pointed out, "We are witnessing a discovery that is opening up a new channel of pharmacological development for the treatment of the progressive phase of Multiple Sclerosis, and with it we want to open a new door on improving the life quality of people who suffer Multiple Sclerosis".
https://www.ehu.eus/en/-/molekula-gako-bat-aurkitu-dute-esklerosi-anizkoitzaren-progresioa-atzeratzeko
http://embomolmed.embopress.org/content/early/2018/07/03/emmm.201708743
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