July 10, 2019 News by Jose Marques Lopes, PhD MS Brain Lesions Linked to Early-life Viral Infection in Mice, Way of Blocking Inflammatory Spread Seen An experimental treatment known as OB-002, that works to block an inflammatory molecule in the brain, prevented the development of lesions there after an early-in-life viral infection in a mouse model of multiple sclerosis (MS). The research āBrain-resident memory T cells generated early in life…
July 9, 2019 News by Ana Pena PhD Cannabidiol-based Oral Treatment Seen to Promote Remyelination in Mice, Trial Planned in MS Patients EHP-101, a cannabidiol-based experimental therapy for multiple sclerosis, was able to recover myelin in damaged nerve fibers and lessen neuroinflammation in a mouse model of MS, data show. Emerald Health Therapeutics, the manufacturer of EHP-101, also announced plans to open Phase 2 clinical trials in patients by…
July 3, 2019 News by Ana Pena PhD NervGen to Advance NVG-291 as Potential Remyelination Therapy for MS NervGen wants to advance the development of NVG-291, its lead investigational therapy for spinal cord damage, as a potential remyelination treatment for multiple sclerosis (MS), the company announced. Following preclinical data showing that NVG-291 promotes myelin repair and regeneration of damaged nerves in animal models of…
July 2, 2019 News by Jose Marques Lopes, PhD Protein Linked to Microglia Cell Activation and Nerve Fiber Damage in Study That Also Notes Potential Treatment A proteinĀ leads to nerve fiber and myelin damage, particularly in progressive forms of multiple sclerosis, by activating brain immune cells called microglia, according to a new study. Its researchers also noted this protein is theĀ target ofĀ experimental MS treatment calledĀ temelimabĀ (GNbAC1), which showed potential in Phase 2 clinical trials. The…
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 30, 2019 News by Alice MelĆ£o, MSc Stem Cells in Mouse Hair Seen to Aid Growth of ‘Dense’ Myelin Sheaths Around Nerve Cells, Study Reports A subset of stem cells in hair follicles, called melanocytes, appear to do more than just give rise to mature melanocytes, cells that help to determine hair color. Those melanocyteĀ stem cells, or McSCs, that carry the CD34 protein were found in hair follicles from mice to differentiate into glia cells…
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 24, 2019 News by Ana Pena PhD Thyroid Hormone Mimetic Holds Promise as Remyelination Therapy for MS, Mouse Study Shows Researchers have developed a compound based on the thyroid hormone T3 that is able to repair damaged myelin in the brain of mice, a discovery that holds promise for healing myelin loss in patients with multiple sclerosis (MS), results of an early study reveal.
April 18, 2019 News by Patricia Inacio, PhD Oligodendrocyte Precursor Cells Disrupt Blood-brain Barrier, Trigger Brain Inflammation in MS, Study Shows Oligodendrocyte precursor cells (OPCs), the cells responsible for myelin production, are unable to migrate into sites of myelin loss in the brain. These cells then cluster and disrupt the blood-brain barrier (BBB), triggering an inflammatory process in the early stages of multiple sclerosis (MS), a study shows. The study, āAberrant oligodendroglialāvascular interactions disrupt the bloodābrain barrier, triggeringĀ CNS inflammation,ā was published in the journalĀ Nature Neuroscience. MS is an autoimmune disease characterized by the loss of myelin (demyelination) ā the fat-rich substance that protects nerve fibers ā which leads to neurodegeneration.Ā Along with loss of myelin, researchers have observed that the blood-brain barrier ā a highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation āĀ breaks down in the initial stages of disease. A team led by researchers at the University of California, San Francisco,Ā have now discovered that OPCs are involved in the disruption of the blood-brain barrier in MS, according to a press releaseĀ from the National MS Society, which funded the study. Oligodendrocytes are myelin-producing cells and are responsible for myelinating the nerve cellsā axons ā a single oligodendrocyte is capable of myelinating multiple axons.Ā Mature myelin-producing oligodendrocytes develop from more immature, stem cell-like OPCs. In a normal brain, upon myelin loss, OPCs are called into action and travel into the damage site where they mature and generate myelin-producing oligodendrocytes. In this study, the researchers found that OPCs in MS form clusters in blood vessels of the brain-blood barrier, having lost the ability to detach from these vessels and migrate to injury sites. In an animal model of MS, they saw that OPC aggregates altered the location of other cells ā called astrocytes ā in a competition for space, and contributed to the disruption of blood vessels. Astrocytes are a group of star-shaped cells, belonging to the group of glial cells, that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation. The team also observed that OPC aggregates trigger an immune inflammatory response, shown by a large number of microglia (the central nervous system immune cells) and immune cells called macrophages around these cell clusters. āWe find in several MS cases, in lesion areas with active inflammation, that OPCs can be found clustered on vasculature, representing a defect in single cell perivascular migration and inability to detach from blood vessels,ā the researchers wrote. Further molecular analysis revealed that OPCs have high levels of Wnt signaling, and elevated secretion of Wif1 factor to the extracellular space thatĀ could explain why OPCs accumulate and destroy the blood-brain barrier. The WiF1 factor is actually a negative regulator of Wnt signaling that is essential for the maintenance of the blood-brain barrierĀ structure. This factor competes with Wnt ligands, and affects the integrity of cellular junctions, making the blood-brain barrier more fragile and permeable. "Evidence for this defective oligodendroglialāvascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB,ā the researchers wrote. They suggested that more studies are needed to better understand the interactions between blood vessels and oligodendrocytes, which could help identify new therapeutic targets for promoting myelin repair in MS.
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…
April 1, 2019 News by Jose Marques Lopes, PhD Tiny DNA Molecule May Help Development of Myelin Repair Therapies, Study Suggests A shortened DNA molecule showed an increased ability to bind myelin in human cells, and may boost the development of remyelination approaches for multiple sclerosis (MS) treatment, according to a study. The study, “Optimization of a 40-mer Antimyelin DNA Aptamer Identifies a 20-mer with Enhanced Properties…
March 21, 2019 News by Santiago Gisler Schwann Cells Stop Blood-clotting Protein Thrombin from Damaging Nerves, Study Finds Schwann cells surrounding neurons protect the degeneration of nerves by blocking thrombin, a blood-clotting protein that can also damage nerves, according to a newĀ study. These findings may aid in the further understanding of genetic and molecular mechanisms behind conditions such asĀ multiple sclerosis (MS). Results of the study,Ā āGlial cells…
March 18, 2019 News by Jose Marques Lopes, PhD Temelimab Provides Long-term Benefits in RRMS Patients, Extension Study Shows Two-year treatment with temelimab reduced brain atrophy, or shrinkage, preserved myelin, and reduced disease progression in patients with relapsing-remitting multiple sclerosisĀ (RRMS), according to findings from an extension study of a Phase 2b clinical trial. Temelimab, previously known as GNbAC1, is a monoclonal antibody that neutralizes the MS-associated human…
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 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 …
January 2, 2019 News by Jose Marques Lopes, PhD Top 10 Multiple Sclerosis Stories of 2018 Multiple Sclerosis News Today brought you daily coverage of key findings, treatment developments, andĀ clinical trials related to multiple sclerosis (MS) throughout 2018. We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2019. Here are the top 10 most-read articles of…
December 17, 2018 News by Iqra Mumal, MSc Inactivation of S1PR2 Protein Shows Therapeutic Potential in MS Mouse Model, Study Reports Inactivation of S1PR2, a cell surface protein, helps improve clinical disability and reduce demyelination in a mouse model of experimental autoimmune encephalitis (EAE), a condition similar to multiple sclerosisĀ (MS) in humans, a study shows. This finding suggests that therapies blocking S1PR2 could have the potential to treat MS. The…
December 10, 2018 News by Patricia Inacio, PhD Microglia Cells Diverse with Distinct Subtypes and Certain Ones May Contribute to Inflammation, Study Finds Microglia, the resident immune cells of the brain, were seen to change throughout the lifespan of mice in a study ā and to be diverse, with distinct cell subtypes. Those with pro-inflammatory behavior may be disease-causing, as they were found to accumulate in the brains of a mouse model of…
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 29, 2018 News by Patricia Inacio, PhD Adult Oligodendrocytes May Replenish Myelin Production in MS, Study Suggests Mature, adult oligodendrocytes can reacquire their ability to produce myelin to replace the ones lost in diseases like multiple sclerosis (MS) without undergoing a stem cell-like state, a new study shows. Myelin is the fat-rich substance that wraps around nerve fiber projections (axons) protecting them and increasing the speed of…
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…
November 1, 2018 News by Ana Pena PhD Stopping Thrombin’s Release in Brain May Prevent Myelin Loss in Diseases Like MS, Mouse Study Suggests Myelin loss might be prevented by astrocytes, a brain cell that regulates myelin’s thickness in coating nerve fibers to support the proper transmission of nerve signals, after astrocytes were seen toĀ block an enzyme called thrombin inĀ a study from the National Institutes of Health (NIH). Its…
October 23, 2018 News by Jose Marques Lopes, PhD Changes in Temperature and Salt Affect Myelin and Raise Risk of MS, Study Says Environmental changes, such as high temperatures and alterations in salt types and concentrations, trigger structural changes to myelin that may increase the risk ofĀ multiple sclerosis (MS), according to a new study. The research, āPathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions,ā was…
October 8, 2018 News by Diogo Pinto National MS Society Awards $12M to 40 Research Projects in US and Elsewhere The National Multiple Sclerosis Society (NMSS)Ā has pledged $12 million to support 40 new, multi-year research projects focused on āstopping MS, restoring lost function, and ending the disease forever,ā the organization announced in a press release. This commitment ā the last allocation set aside for research in 2018 ā…