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One size does not fit all
May 26, 2009A new look at therapies
Statins, a commonly prescribed class of drugs used by millions worldwide to effectively lower blood cholesterol levels, may actually have a negative impact in Multiple Sclerosis (MS) patients treated with high daily dosages.
A new study by researchers at the Montreal Neurological Institute (MNI), McGill University, demonstrates that statin therapy in mice inhibits myelin repair or remyelination in the central nervous system. The findings, published in The American Journal of Pathology, highlight the crucial need to monitor the effects of central nervous system-accessible immune therapies on the myelin repair processes in patients with MS and other progressive demyelinating diseases.
Canadians have one of the highest rates of MS in the world. An estimated 50, 000 Canadians have MS, with approximately 1,000 new cases diagnosed each year. MS is an autoimmune disease of the central nervous system (CNS), in which immune cells attack the myelin sheath (the protective insulation of nerve fibres), and the myelin-producing cells of the CNS (oligodendrocytes), causing demyelination. This causes damage which disrupts the nerve cell's ability to transmit signals throughout the nervous system.
In the early stages of MS, following an immune system attack on myelin, oligodendrocyte progenitor cells or stem cells in the CNS are recruited to the lesion. These cells mature and produce new myelin to repair the damage.
"Statins, which are known to modify the immune system response and have a wide array of effects on other cellular processes, were propelled into clinical trials based on studies in an animal model of MS indicating a reduction in clinical disease severity," says Dr. Veronique Miron, post-doctoral fellow in Dr. Jack Antel's lab at the MNI, and lead investigator in the study. "The mechanism of statin action in these studies was not determined. That is, does statin directly effect myelin and/or the oligodendrocytes or is disease severity reduced indirectly due to the dampening of the immune response. This issue required further investigation, particularly due to the ability of statins to cross the blood-brain barrier and access the CNS, and the enrichment of cholesterol in the myelin sheath."
The objective of the MNI study was to determine the direct impact of simvastatin, a statin in clinical trials, on the integrity of myelin in the brain and on the remyelination process. The study uses a model of myelin damage that has relatively little inflammation and mimics the demyelinating aspect of MS, allowing MNI researchers to determine the direct effect of long-term statin therapy on remyelination, independent of its indirect effects mediated via immune modulation.
"The results of our study indicate that simvastatin has in fact, a slightly deleterious effect on myelin under non-pathological conditions," adds Dr. Miron. "During remyelination, there is a decrease not only in myelin production but also in oligodendrocyte number as a result of simvastatin treatment. The findings also suggest that simvastatin inhibits CNS remyelination by blocking oligodendrocyte progenitor cell differentiation or maturation into myelinating oligodendrocytes."
This study underscores the necessity of monitoring the long-terms effects of CNS accessible immune therapies, particularly those that can impact cell types that are postulated to be targeted in neurological disease processes and that are implicated in any brain tissue repair processes. Understanding the underlying mechanisms of these therapies will lead to improved and enhanced treatment strategies and ultimately improved quality of life for people who suffer from a variety of neurological diseases.
McGill University
Canadians have one of the highest rates of MS in the world. An estimated 50, 000 Canadians have MS, with approximately 1,000 new cases diagnosed each year. MS is an autoimmune disease of the central nervous system (CNS), in which immune cells attack the myelin sheath (the protective insulation of nerve fibres), and the myelin-producing cells of the CNS (oligodendrocytes), causing demyelination. This causes damage which disrupts the nerve cell's ability to transmit signals throughout the nervous system.
In the early stages of MS, following an immune system attack on myelin, oligodendrocyte progenitor cells or stem cells in the CNS are recruited to the lesion. These cells mature and produce new myelin to repair the damage.
"Statins, which are known to modify the immune system response and have a wide array of effects on other cellular processes, were propelled into clinical trials based on studies in an animal model of MS indicating a reduction in clinical disease severity," says Dr. Veronique Miron, post-doctoral fellow in Dr. Jack Antel's lab at the MNI, and lead investigator in the study. "The mechanism of statin action in these studies was not determined. That is, does statin directly effect myelin and/or the oligodendrocytes or is disease severity reduced indirectly due to the dampening of the immune response. This issue required further investigation, particularly due to the ability of statins to cross the blood-brain barrier and access the CNS, and the enrichment of cholesterol in the myelin sheath."
The objective of the MNI study was to determine the direct impact of simvastatin, a statin in clinical trials, on the integrity of myelin in the brain and on the remyelination process. The study uses a model of myelin damage that has relatively little inflammation and mimics the demyelinating aspect of MS, allowing MNI researchers to determine the direct effect of long-term statin therapy on remyelination, independent of its indirect effects mediated via immune modulation.
"The results of our study indicate that simvastatin has in fact, a slightly deleterious effect on myelin under non-pathological conditions," adds Dr. Miron. "During remyelination, there is a decrease not only in myelin production but also in oligodendrocyte number as a result of simvastatin treatment. The findings also suggest that simvastatin inhibits CNS remyelination by blocking oligodendrocyte progenitor cell differentiation or maturation into myelinating oligodendrocytes."
This study underscores the necessity of monitoring the long-terms effects of CNS accessible immune therapies, particularly those that can impact cell types that are postulated to be targeted in neurological disease processes and that are implicated in any brain tissue repair processes. Understanding the underlying mechanisms of these therapies will lead to improved and enhanced treatment strategies and ultimately improved quality of life for people who suffer from a variety of neurological diseases.
McGill University
Remyelination Current Events and Remyelination News RSSNew clue into how brain stem cells develop into cells which repair damaged tissue
The joint research, funded by the National Multiple Sclerosis Society and the UK MS Society as well as the National Institutes of Health and Howard Hughes Medical Institute, was conducted by scientists at the University of California San Francisco (UCSF) and University of Cambridge and was published today (01 July) in the journal Genes and Development.
UCF team's advanced nerve cell system could help cure diabetic neuropathy, related diseases
Multiple sclerosis, diabetic neuropathy, and other conditions caused by a loss of myelin insulation around nerves can be debilitating and even deadly, but adequate treatments do not yet exist.
In the war against diseases, nerve cells need their armor
In a new study, researchers at the Montreal Neurological Institute (MNI), McGill University, and the Université de Montréal have discovered an essential mechanism for the maintenance of the normal structure of myelin, the protective covering that insulates and supports nerve cells (neurons).
Intraspinal implant of mesenchymal stem cells may not heal the demyelinated spinal cord
Multiple sclerosis is a disease caused by the loss of the myelinated sheath surrounding the nerve fibers of the spinal cord.
Multiple Sclerosis: new MRI contrast medium enables early diagnosis in animal model
In an animal model of multiple sclerosis (MS), neuroradiologists and neurologists of the University hospitals of Heidelberg and Würzburg have been able to visualize inflammatory tissue damage, most of which had remained unrecognized up to now, with the aid of a new contrast medium, Gadofluorine M, in magnetic resonance imaging.
Rutgers University Scientist's Research Reveals Critical Knowledge About the Nervous System
Uncover the neural communication links involved in myelination, the process of protecting a nerve's axon, and it may become possible to reverse the breakdown of the nervous system's electrical transmissions in such disorders as multiple sclerosis, spinal cord injuries, diabetes and cancers of the nervous system.
Antibody leads to repair of myelin sheath in lab study of multiple sclerosis and related disorders
Mayo Clinic researchers have found that a human antibody administered in a single low dose in laboratory mouse models can repair myelin, the insulating covering of nerves that when damaged can lead to multiple sclerosis and other disorders of the central nervous system.
Pregnancy hormone increases nerve cells' insulation, restores damage
A hormone produced during pregnancy spontaneously increases myelin, which enhances signaling within the nervous system, and helps repair damage in the brain and spinal cord.
Study establishes safety of spinal cord stem cell transplantation
Transplanting human embryonic stem cells does not cause harm and can be used as a therapeutic strategy for the treatment of acute spinal cord injury.
More Remyelination Current Events and Remyelination News Articles
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Molecular Signaling and Regulation in Glial Cells: A Key to Remyelination and Functional Repair by Jeserich (Editor), Hans H. Althaus (Editor), C. Richter-Landsberg (Editor), R. Heumann (Editor) An excellent survey of the most recent advances in the area of cellular and molecular biology of glial cells and their involvement in remyelination and functional repair in the CNS. A major part of this book deals with signaling paths within and among neural cells. Glial cells (astrocytes, oligodentrocytes, microglial cells) themselves release substantial amounts of cytokines, growth factors and other signaling molecules, which play an important role during injury and regeneration. Another signaling route between neurons and glial cells follows ion channels and neurotransmitter receptors. In addition to animal models, human oligodentrocytes in cell culture and in the human MS brain are characterized with respect to their immunocytochemistry and function. |
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Advances in Multiple Sclerosis and Experimental Demyelinating Diseases (Current Topics in Microbiology and Immunology) by Moses Rodriguez (Author), Moses Rodriguez (Editor) There is a need for a paradigm shift in our thinking about the pathogenesis of multiple sclerosis. Challenging Charcot s hypothesis that inflammatory response is the primary contributor to demyelination, Dr. Rodriguez and colleagues take a fresh, bold look at the causes and possible treatments of MS. Assuming oligodendrocyte injury as a prerequisite to MS, the authors explore viruses, toxins and genetic defects as possible culprits. They present novel methods to interrupt and reverse demyelination. This book examines the correlation between axonal loss and clinical deficits, including the implied role of the CD8+ T cell and perforin. It assesses proteases, specifically, kallikrein 6, which are strongly associated with active demyelination. By directing natural... |
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