Multiple sclerosis (MS) is an autoimmune disease in which the myelin, or fatty coating of nerve cells, is eroded away, causing nerve damage and slower signaling between the brain and body. Symptoms of MS range from blurred vision, various forms of peripheral pain to complete paralysis, and while treatments exist, the causes are not fully understood and there is nothing to reverse the disease process. In new research published in Stem Cell ReportsAnastassia Voronova, associate professor of nerve stem cell biology at the University of Alberta, is one step closer to demonstrating the potential of a brain molecule called fractalquine to halt and even reverse the effects of multiple sclerosis and other neurodegenerative diseases. She injected fractalquine into mice with chemically induced MS and found that it increased the number of new oligodendrocytes, specialized myelin-producing cells in both the embryonic and adult brains, that are damaged during the autoimmune attack of MS.
The fates of oligodendrocyte precursors, such as survival, proliferation, and differentiation, are important for efficient oligodendrocyte generation and are regulated by neighboring cells, such as microglia. While microglia can adopt a wide range of activation states, in general microglia can be detrimental to regeneration through the release of pro-inflammatory cytokines or beneficial by shedding myelin debris and/or secreting anti-inflammatory and regenerative proteins. The recurrent oligos are not only regulated by growth factors (e.g. bFGF or PDGF) but also by chemokines, such as the neuron-secreted fractalquine (CX3CL1/FKN). FKN signals through its single receptor, CX3CR1, which is expressed at high levels in microglia and at lower levels in OPCs. While the role of FKN signaling in adult parenchymal OPCs is unknown, it has previously been shown that mice with Cx3cr1 KO (knockout) or with reduced levels of Cx3cr1 in cortical progenitors, have impaired production of developmental oligodendrocytes.
Furthermore, demyelinated Cx3cr1 KO mice show poor remyelination, impaired microglial clearance, and reduced migration and proliferation of precursor oligos. Voronova’s previous research tested the safety and efficacy of fractalquine in normal mice and found similar beneficial effects. Other researchers have shown that fractalquine can provide nerve protection in mouse models before the disease is induced, but this is the first time it has been tested in animals that already have the disease. Voronova and her team observed new oligodendrocytes, as well as reactivated progenitor cells that can regenerate oligodendrocytes, in the brains of treated animals. Remyelination occurred in both white and gray matter. The researchers also observed a reduction in inflammation, part of the damage done by the immune system. Next steps for treatment include testing in other diseased mouse models, including those with neurodegenerative diseases other than MS.
- By Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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by Almeida MMA et al. Cell Reports 2023 Dec 27 in press.
J Neurochem. 2022; 162(5):430-443.
Stem Cell Reports. 2021; 16(8):1968-84.
– Degree in Medicine and Surgery in 1998 (MD Degree in 1998) – Specialist in Clinical Biochemistry in 2002 (Clinical Biochemistry residency in 2002) – Doctorate in Neurobiology in 2006 (Neurobiology PhD in 2006) – Stayed in the United States, Baltimore (MD ) as a researcher employed by the National Institute on Drug Abuse (NIDA/NIH) and then at Johns Hopkins University, from 2004 to 2008. – Since 2009 he has been involved in Personalized Medicine. – Emergency medical care in private structures since 2010 – Holder of two patents on the preparation of gluten-free products starting from regular enzymatically neutralized wheat flour (owner of patents concerning the production of gluten-free bakery products, starting from regular wheat flour). – Head of the Research and Development department for CoFood srl (Leader of the R&D for the partnership CoFood srl) – Author of articles on medical and health information on the website www.medicomunicare.it (Medical/health information on website) – Author of ECM FAD courses advertised on the website www.salutesicilia.it