May 21, 2020 News by InĆŖs Martins, PhD Learning Physical Task Seen to Trigger Myelin Repair in MS Mouse Model Movements that are an act of “learning” motor tasks after lesions appearĀ in the protective myelin sheath of neurons seem to induce both new and existing oligodendrocytes ā the cells that make up myelin ā to repair those lesions, a study in mice shows. Precisely timed rehabilitation programs and exercise may…
May 13, 2020 News by InĆŖs Martins, PhD Ian Duncan Awarded 2020 Dystel Prize for Discoveries in Myelin Repair Neuroscientist Ian D. DuncanĀ has been awarded the 2020 John Dystel Prize for Multiple Sclerosis Research for work that advanced understanding of how myelin, the protective sheath surrounding nerve cells, can be repaired in diseases like multiple sclerosis (MS). āProfessor Duncan has made a series of critical research advances…
April 9, 2020 News by Joana Carvalho, PhD Ursolic Acid, Compound in Fruit Peels, Promotes Myelin Repair, Early Study Finds Ursolic acid, a compound found in some herbs and in the peels of certain fruits, promoted nerve cell repair and restored the myelin sheath covering and protecting nerve endings in a mouse model of multiple sclerosis (MS), a study reported. Due to its strong anti-inflammatory and immunomodulatory…
April 8, 2020 News by Patricia Inacio, PhD Small Changes in Genes May Affect Myelin Production, Study Suggests The small variants seen in the DNA code among individuals may affect the ability of oligodendrocytes to produce myelin, the protective coat surrounding neurons and whose destruction is a hallmark of multiple sclerosis (MS), a study reported. These findings open the possibility of new therapeutic options that target the…
February 28, 2020 News by Ana Pena PhD #ACTRIMS2020 – Remyelination in Adult Animal Brains Possible via Cell Transplant, Study Says Transplanting humanĀ glial progenitor cells (GPCs) ā brain cells able to generate myelin-producing cells ā effectively led to remyelination in the brains of adult mice with myelin disorders, a study found. These results were presented atĀ the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020, running…
February 26, 2020 News by Margarida Azevedo, MSc Potential Therapy, Anavex 2-73, Shows Ability to Protect Neurons and Promote Myelin in Early Tests Anavex Life Sciences‘ investigational therapy Anavex 2-73 (blarcamesine) showed an ability to protect, repair, and induce the formation of oligodendrocytes ā the cells that produce the protective myelin layer around neurons ā in early cell testing, researchers reported. These findings, which further establish the therapy’s potential as a treatment…
February 20, 2020 News by Iqra Mumal, MSc #ACTRIMS2020 ā Keynote SpeakerĀ Peter Calabresi to Discuss Link Between Genetics and MS Severity Specific mutations in genes that provide instructions to make two proteins ā Ā called C3 and C1q ā are linked to increased severity of multiple sclerosis (MS), according to new research. The new finding will be presented by Johns Hopkins University School of MedicineĀ researcher Peter Calabresi, MD, during…
February 13, 2020 News by Ana Pena PhD Gold Nanocrystals in Phase 2 Testing Show ‘Robust’ Remyelination Potential in Animal Models Clene Nanomedicine‘s remyelination therapy candidate, CNM-Au8, showed a “robust” ability to stimulate the production of new myelin and increase the number of myelin-wrapped nerve fibers in the brain and spinal cord of animals in models of demyelinating disease, allowing mice to recover motor skills, a study reports.
January 20, 2020 Columns by Ed Tobias MS News that Caught My Eye Last Week: High Cost of MS Meds; MS Progression, Relapse, and DMT Timing; Remyelinating Therapy Trial; Myelin Regeneration Mouse Study Almost Half of MS Patients Change or Stop DMT Due to High Financial Burden, Survey Shows I frequently see reports of this on multiple sclerosis patient websites. People with MS say they’ve been forced to change or even stop their treatment because it costs too much. Some people have…
January 14, 2020 News by Patricia Inacio, PhD New Mechanism Boosting Myelin Regeneration May Ease MS Symptoms, Mouse Study Shows Blocking a protein called PAR1 may enhance the regeneration of myelin, the protective fatty layer that covers nerve fibers and isĀ damaged in multiple sclerosis (MS), a mouse study shows. Therapeutic targeting of PAR1 may promote remyelination and delay MS progression, according to the study, āBlocking the Thrombin Receptor…
January 2, 2020 News by Ana Pena PhD Top 10 Multiple Sclerosis Stories of 2019 Throughout 2019, Multiple Sclerosis News Today brought you daily coverage of the latest scientific findings, treatment developments, and clinical trialsĀ related toĀ multiple sclerosis (MS). We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2020. Here are the top 10 most-read articles of…
October 14, 2019 News by Marisa Wexler, MS Metformin Works to Promote Remyelination in Ways Similar to Fasting, Study Says Metformin, a common diabetes treatment that works to mimic dietary fasting, was seen to promote remyelination in the stem cells of elderly rats, suggesting it may be useful in treating multiple sclerosis. “Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells” was published in…
September 9, 2019 News by Marta Figueiredo, PhD Inflammation Hijacks Myelin Repair Cells to Promote Immune Attacks, Study Shows Brain inflammation in multiple sclerosisĀ (MS) hijacks immature myelin repair cells, not only preventing myelin restoration but also promoting sustained inflammation and immune attacks against myelin, a preclinical study shows.
May 2, 2019 News by Patricia Inacio, PhD Estrogen Promotes Remyelination in Adult Brains of MS Mice, Study Shows Giving estrogen to two different adult mouse models of multiple sclerosis (MS), including the experimental autoimmuneĀ encephalomyelitis (EAE) model, promoted remyelination, a new study shows. Exposure to the hormone affected gene activity in oligodendrocytes, tricking them into producing myelin (the fatty substance that protects nerve cells, and that is destroyed…
April 26, 2019 News by Marisa Wexler, MS Cellular Senescence Implicated in MS Development, Study Suggests Cellular senescence ā the process of aging at the cellular level ā may play a role in the development of primary progressive multiple sclerosis (PPMS) by limiting the ability of myelin-producing cells (oligodendrocytes) to renew and mature. The study with that finding, “Cellular senescence in progenitor…
April 12, 2019 News by Jonathan Grinstein TMEM10 in Demyelinated MS Lesions May Contribute to Remyelination, Study Suggests A protein that promotes nervous system repair through remyelination ā the creation of myelin, the protective sheath around nerve cells ā in mice also is found in remyelinating plaques in brains of multiple sclerosis (MS) patients, new research shows. This protein potentially represents a new therapeutic target in demyelinating…
February 22, 2019 News by Iqra Mumal, MSc New Compounds Offer Significant Anti-inflammatory, Neuroprotective Benefits in MS Mouse Study Two newly identified variants of the known pharmaceutical agent chloroindazole showed significant anti-inflammatory and neuroprotective benefits in a mouse model of multiple sclerosis, a new study shows. Multiple sclerosis is an autoimmune, demyelinating disease of the central nervous system with no known cause or cure. Patients with MS characteristically show loss of the myelin sheath, a protective coat in nerve cells that helps increase cell-to-cell signaling. Several studies have suggested that estrogens ā a type of hormone ā are beneficial to the functioning of the central nervous system, and help regulate the immune system. Thus, they are attractive candidates for the treatment of MS. However, despite their potential to treat MS, estrogen-based therapies can have several undesirable side effects, such as feminizing male recipients and increasing the risk of developing breast and endometrial cancers in females. Interestingly, estrogens work by binding and activating two different types of receptors: the estrogen receptor (ER)Ī± and ERĪ². The cancer-inducing effects of estrogens are mediated mainly through estrogen receptor ERĪ±. Hence, therapies that specifically target ERĪ² can bypass these deleterious effects. Chloroindazole (IndCl), a pharmaceutical agent, has up to 100-fold relative binding affinity for ERĪ² over ERĪ±. IndCl has been shown previously to have beneficial effects on modulating the immune system and the central nervous system, and inducing myelination of nerve cells in mouse models of MS. Furthermore, IndCl and other ERĪ²-activating agents directly support the growth, differentiation (maturation), and overall myelination activity of oligodendrocytes, which are the nerve cells that produce the myelin sheath. Therefore, in order to optimize the benefits of IndCl, researchers developed and screened seven novel IndCl analogues for their ability to promote oligodendrocyte survival, growth, and differentiation. These analogues have a molecular structure closely similar to that of IndCl, but interact with estrogen receptors in subtly different ways. Among these seven compounds, researchers found two analogues ā IndCl-o-chloro and IndCl-o-methyl ā that stimulated growth and differentiation similar to the original IndCl. Next, researchers evaluated the benefits of these compounds in a mouse model of MS ā the experimental autoimmune encephalomyelitis (EAE) mouse model ā to determine whether they could alter the disease course, white matter pathology (level of demyelination), and inflammation. Results indicated that both compounds āameliorated disease severity, increased mature OLs [oligodendrocytes], and improved overall myelination in the corpus callosum and white matter tracts of the spinal cord,ā researchers wrote. Corpus callosum is a thick band of nerves that connect the left and right side of the brain. White matter tracts connect the cortex (the largest part of the brain) with other areas in the central nervous system. These beneficial effects were accompanied by a reduced production of the toxic, inflammatory molecules interferon-Ī³ and CXCL10. Additionally, IndCl-o-methyl also reduced the levels of peripheral interleukin (IL)-17, a molecule that strongly induces inflammation. Furthermore, IndCl and both analogues upregulated the expression of a compound called CXCL1, which is associated with increased production of oligodendrocytes. Not only were these two newly identified compounds equivalent to IndCl, but the two analogues performed better in reducing disability and encouraging remyelination than the original compound, and without any obvious side effects. āTheĀ o-Methyl andĀ o-Chloro IndCl analogues represent a class of ERĪ² ligands that offer significant remyelination and neuroprotection, as well as modulation of the immune system; hence, they appear appropriate to consider further for therapeutic development in multiple sclerosis and other demyelinating diseases,ā the researchers concluded. āWe believe we created a drug that does two things really well, modulating inflammation and allowing axon remyelination. No other drug on the market can do these two things simultaneously,ā Seema K. Tiwari-Woodruff, said in a press releaseĀ written by Stacy Kish. Tiwari-Woodruff is the study's lead author. āThe most amazing part of the study is that these new analogues of a known estrogen modulator, chloroindazole, are superior in treating mouse model of multiple sclerosis,ā she added. The team has patented the analogues, and hopes to begin further pharmacological and toxicity studies soon.
February 21, 2019 Columns by Tamara Sellman Need to Know: What Is Remyelination? Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about MS? Visit our forum. This week’s question is inspired by the forum topicĀ “New MS Therapy Company to Focus on Rejuvenating Coating…
February 6, 2019 News by Patricia Inacio, PhD New Research About RhoE Protein Sheds Light on Two Problematic Processes in MS The RhoE protein has been identified as being important for axons’ Ā myelination and extension in the central nervous system, two processes that go awry in diseases like multiple sclerosis (MS). The findings stem from Pilar Madrigalās doctoral thesis, āRole of the small GTPase RhoE in myelination and axonal tracts development.ā…
February 4, 2019 Columns by Ed Tobias MS News that Caught My Eye Last Week: MS Pain Research, Myelin Studies, Antibody Trial MS Patients Sought to Test Alternative Chronic Pain Treatment Methods Do you have serious pain issues along with your MS? If so, you might be interested in this study that’s looking for participants. By the way, who says that pain isn’t an MS symptom? A clinical trial…
January 30, 2019 News by Patricia Inacio, PhD Brain Cells Key to Myelin Grown in Lab and Show Long-Term Survival Essential to Research, Study Reports Stem cells tweaked in the laboratory have allowed researchers, reportedly for a first time, to generate and maintain ball-shaped cultures ā called spheroids ā of human brain cells in 3D that contain oligodendrocytes, the cells that produce myelin, alongĀ with neurons and the astrocytes that are essential to nerve cell health.
January 28, 2019 News by Jonathan Grinstein Altered Oligodendrocyte Diversity Contributes to Multiple Sclerosis, Study Suggests Subpopulations of oligodendrocytes ā cells that produce the myelin sheath that protects nerve fibers ā are altered in patients withĀ multiple sclerosis, a study shows. These findings suggest that oligodendrocyte diversity and the different functions of these subpopulations might have a greater role in the disease than previously thought. The severity of MS varies greatly, and the patient's disability level does not correlate well with the degree of myelin loss. This suggests that other factors contribute to MS severity. One such factor may be that oligodendrocytes are heterogeneous ā diverse in makeup and function. For example, oligodendrocytes in mouse spinal cords are known to naturally produce longer myelin sheaths than oligodendrocytes in the mouse brain. Additionally, individual oligodendrocytes have been shown to have different molecular makeups. However, the extent of human oligodendrocyte diversity and its possible contribution to MS pathology remains unknown. Researchers from the Karolinska Institutet and the MRC Centre for Regenerative Medicine studied the differences of individual human oligodendrocytes from healthy and MS brains to assess their diversity. Specifically, the team examined oligodendrocytes from the white matter areas of post-mortem human brains both from MS and non-MS patients. The team examined the RNA content ā the messenger molecule carrying instructions from DNA for the production of proteins ā from individual oligodendrocytes. Researchers identified groups of RNA molecules that defined features of oligodendrocytes from healthy human white matter. Some of these groups match those that defined oligodendrocytes in healthy mice. Strikingly, some of these RNA molecules in healthy brains were under-represented in oligodendrocytes from MS brains, whereas others were more prevalent. āWe found that oligodendrocytes are a diverse population of cells and that different types are likely to have different functions in the brain,ā Charles ffrench-Constant, the study's co-lead author, said in a Karolinska InstitutetĀ news release written byĀ Katarina Sternudd. These differences in oligodendrocyte RNA content may indicate different functional states of oligodendrocytes in MS lesions. āThe proportions of different resident oligodendrocytes in the lesions are changed, along with their properties, suggesting that they might have important roles in MS,ā said Eneritz Agirre, PhD, a study co-author. Furthermore, the researchers believe that this altered diversity in oligodendrocytes in MS may be important to understand disease progression and develop therapeutic approaches. āUnderstanding which types of oligodendrocytes are most beneficial in repairing myelin will be crucial for maximizing the chances of developing much-needed treatments for MS,ā said Anna Williams, PhD, study co-lead author. The team concluded that theĀ changes in different oligodendrocyte subpopulations in MS suggest "a more complex role of these cells in the pathology of the disease, but also in regeneration of new cells,ā said GonƧalo Castelo-Branco, PhD, another study co-lead author.
January 25, 2019 News by Jose Marques Lopes, PhD Chi3l3 Protein Favors Production of Myelin Repair Cells, Mouse Study Determines A protein marker for activated immune cells called Chi3I3 is key for the production of myelin-forming cells, and may become a target to boost myelin repair in multiple sclerosis (MS), according to a new study. The research, āChi3l3 induces oligodendrogenesis in an experimental model of autoimmune…
January 18, 2019 News by Jonathan Grinstein Small Molecule Shows Ability to Limit Autoimmune Response in MS, Mouse Study Reports A small molecule called Sephin1 may be able to significantly delay harm to neurons in multiple sclerosisĀ (MS) by protecting oligodendrocytes, limiting the autoimmune response, a mouse study reports. The study, āSephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis,ā was published in the journalĀ Brain. MS is thought to be caused by immune-mediated inflammation that damages the myelin ā an insulating sheath around nerve cells. For this reason, current MS disease-modifying treatments focus on immune-mediated inflammation. Although these treatments moderate disease relapses, their impact on disease progression is unclear. Previous studies have demonstrated that oligodendrocytes ā cells that produce myelin ā are critical in protecting against neuron demyelination and axon (nerve fiber) damage. As a result, researchers have been keen to develop alternative therapeutic approaches that protect oligodendrocytes, and ultimately limit disease progression.Ā A signaling pathway called integrated stress response that acts as a natural defense system to protect cells has been shown to reduce the inflammatory impact on oligodendrocytes. This response is triggered byĀ phosphorylation (a chemical reaction) of a protein called eukaryotic initiationĀ factor 2 alpha (eIF2Ī±),Ā and reduces the total production of proteins, instead promoting the synthesis of protective proteins in the cells. Conversely, the integrated stress response can be cut off by dephosphorylation of eIF2Ī±. Sephin1 was shown to inhibit the dephosphorylation of eIF2Ī±, prolonging the protective response. In this study, researchers at theĀ University of Chicago proposed thatĀ Sephin1, by producing this response, could protect oligodendrocytes and slow the progress of the disease. The team tested their hypothesis in a mouse model called experimental autoimmune encephalomyelitis (EAE), which is similar to MS in humans. Results showed that treatment withĀ Sephin1 did inhibit eIF2Ī±Ā dephosphorylation in EAE mice, triggeringĀ a protective response against inflammation. More importantly, myelin-producing oligodendrocytes were also protected, and disease onset was significantly delayed. This correlated with diminished oligodendrocyte loss, protected neuronal axons and myelin, and prolonged integrated stress response. In addition, Sephin1 decreased the levels of inflammatory immune T-cells, and the production of inflammatory signals within the central nervous system. "By protecting oligodendrocytes and diminishing demyelination, we also reduce the generation of myelin debris," Ā Brian Popko, PhD, the study's senior author, said in a press release. "The decreased exposure to myelin fragments should also limit the auto-immune response."Ā Popko is the Jack Miller professor of neurological disorders, and director of the Center for Peripheral Neuropathy at the University of Chicago. The effects of Sephin1 were also combined with interferon-beta treatment ā an anti-inflammatory first-line MS therapy. Researchers found that the combination was more effective than the therapies given separately. "Encouragingly, adding Sephin1 to the established anti-inflammatory MS drug interferon beta provided additive benefits to the mouse MS model," said study co-author Yanan Chen, PhD,Ā a postdoctoral fellow in the Popko laboratory. The team concluded that the results "suggest that a neuroprotective treatment based on the enhancement of the integrated stress response would likely have significant therapeutic value for multiple sclerosis patients." Treatment withĀ Sephin1, they say, "could lead to a better clinical outcome in multiple sclerosis patients as a safe neuroprotective drug, perhaps when used in combination with immune-modulatory therapies." Sephin1 has been patented and licensed to InFlectis BioScience, a French biotech company.
January 3, 2019 News by Patricia Inacio, PhD Excess of Single Transcription Factor Appears to Hinder Myelin Repair by Oligodendrocytes, Study Finds Unusually high levels of a transcription factor called paired related homeobox protein 1 (PRRX1) in human oligodendrocyte progenitor cells hinders their ability to respond to the loss of myelin and to transform into mature, myelin-producing oligodendrocytes, a new study shows. These findings suggest a new potential way of treatingĀ …
December 4, 2018 News by Patricia Inacio, PhD Small Molecule Linked to Cells That Control Myelin Production and Repair in Study The formation of new myelin sheaths by oligodendrocytes is impaired in the absence of a small molecule, called Vav3, that oversees pathways regulating the shape of oligodendrocytes, new study reports. Its researchers pinpoint Vav3 as a potential therapeutic target to improve and speed myelin repair in diseases like multiple sclerosis…
November 19, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: New Thinking About MS Development, Rhythm to Improve Walking, UK Nurse Shortage, B-cells MS-specific Lineage of Oligodendrocytes May Provide New Hints on MS Development Our immune system, according to this study, may not be the only thing playing a role in the development of our MS. The same cells that produce the myelin that coats our nerves may also be…
November 15, 2018 News by Ana Pena PhD MS-specific Lineage of Oligodendrocytes May Provide New Hints on MS Development The cells that produce myelin in the brain and spinal cord, called oligodendrocytes, may play an active role in the onset or progression of multiple sclerosis (MS), according to a study combining data from MS mouse models and the human brain. This discovery supports the…
September 24, 2018 News by Jose Marques Lopes, PhD Oligodendrocytes, Cells That Produce Myelin, Can Be Generated from Astrocytes, Study Reports A molecule known as Sox10 enables brain cells called astrocytes to convert into myelin-forming oligodendrocytes, a new study in mice reports. The findings suggest an approach for myelin repair in patients with multiple sclerosis (MS) and similar disorders, its researchers said. The study, āIn vivoĀ conversion of…
August 29, 2018 News by Patricia Inacio, PhD Small Molecule TDP6 Activates Myelin Regeneration in Mice with MS, Other Diseases, Study Finds A small synthetic molecule called TDP6 mimics a natural growth factor and promotes myelin regeneration in a mouse model of demyelination diseases such asĀ multiple sclerosis (MS), a new study from Australia shows. TDP6 works by targeting a receptor at the surface of myelin-producing cells called oligodendrocytes. The study, ā…