A new small molecule offers interesting results in limiting neurodegeneration and relieving the characteristic symptoms of multiple sclerosis. Studied in mouse models, the advance could lead to clinical trials in humans.
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Multiple sclerosis (MS) is a progressive, autoimmune neurological disease for which there is currently no treatment. curativecurative. Its symptoms greatly hamper the quality of life of patients, who suffer from coordination and cognition problems, muscle weakness — even paralysis — and depression.
It should be noted that all current drug treatments against MS target the immune system, for the simple reason that this would be theinflammationinflammation of the immune system which would damage myelin. The latter is a protective sheath which forms around the nerve fibersnerve fibers in the brainbrain and the spinal cordspinal cordproviding a insulationinsulation electrical which accelerates the conduction of signals throughout the central nervous systemcentral nervous system and peripheral. Yet research shows that it is possible that the relationship runs the other way, that neurodegeneration precedes the autoimmune response.
Identification of a small neuroprotective molecule
Based on this hypothesis, researchers from the Canadian Center for Addiction and Mental Health (CAMH) conducted preclinical studies on mice, targeting the brain system. glutamateglutamate. Indeed, there is a process (glutamate excitotoxicity) during which this neurotransmitterneurotransmitter leads to degeneration of neuronsneurons which would disrupt myelination. “ Thus, glutamate receptor antagonists preventing excitotoxicity have shown promise in animal models of MS, although blocking glutamate signaling prevents essential neuronal functions », underline the authors of the new study published in Science Advances.
First, the researchers identified a subunitsubunit of the AMPA receptor — to which glutamate binds — particularly involved in the loss of neurons and myelination. Then, they analyzed a series of moleculesmolecules likely to inhibit the subunit in question to leave only one small molecule. The lucky one contributes to the neuroprotection of cells and has been shown to be effective in treating nerve damage and symptoms.
Towards clinical use?
“ Our compound had a stunning effect on saving the myelinmyelin and motor function in laboratory models, and I hope these effects will translate to the clinic to complement current treatments and bring new hope to MS patients said Dr. Fang Liu, researcher at CAMH. The compound could prove useful as an alternative or complementary treatment to therapiestherapies existing, believes the researcher. “ As with cancer chemotherapy drug cocktails, simultaneous targeting of pathways pathologicalpathological of MS at several points can have synergistic effects and achieve better results. »
This first preclinical phase provided evidence of the effectiveness and tolerability of the small molecule on mouse modelsmouse models. The next steps in drug development will include further preclinical research, including the safety and stability of the compound. Perhaps next will come clinical testsclinical tests on Man.
