Posts tagged MS
Articles and news from the latest research reports.
Finding challenges accepted view of MS: Unexpectedly, damaged nerve fibers survive
Multiple sclerosis, a brain disease that affects over 400,000 Americans, causes movement difficulties and many neurologic symptoms. MS has two key elements: The nerves that direct muscular movement lose their electrical insulation (the myelin sheath) and cannot transmit signals as effectively. And many of the long nerve fibers, called axons, degenerate.
Many scientists believe that axons are doomed once they lose the insulation, but a new study by graduate student Chelsey Smith and former undergraduate Elizabeth Cooksey in the Journal of Neuroscience shows axons can survive for long periods in rats even after losing myelin.
"This was the first study to demonstrate long-term axon survival after myelin deterioration," says senior author Ian Duncan, a professor in the School of Veterinary Medicine at the University of Wisconsin-Madison.
The mutant rats in the experiment have substantial myelin at first, but by eight weeks the essential myelin insulation is lost. “It was surprising,” says Duncan, an expert in MS pathology. “Nine months is a relatively long period in a rat’s lifetime, and there wasn’t a loss of axons, so the assumption that axons must automatically die without myelin seems incorrect.”
One in Three Children with Multiple Sclerosis has Cognitive Impairment
Data from the largest multicenter study accessing cognitive functioning in children with multiple sclerosis (MS) reveals that one-third of these patients have cognitive impairment, according to a research paper published in the Journal of Child Neurology. Led by Lauren B. Krupp, MD, Director of the Lourie Center for Pediatric Multiple Sclerosis at Stony Brook Long Island Children’s Hospital, the study indicates that patients experience a range of problems related to cognition.
In “Cognitive Impairment Occurs in Children and Adolescents with Multiple Sclerosis: Results from a United States Network,” Dr. Krupp and colleagues from Stony Brook and five other national Pediatric MS Centers of Excellence measured the cognitive functioning of 187 children and adolescents with MS, and 44 who experienced their first neurologic episode (clinically isolated syndrome) indicative of MS. They found that 35 percent of the patients with MS and 18 percent of those with clinically isolated syndrome met criteria for cognitive impairment. All patients were under age 18 with an average disease duration of about two years.
“This study is important because it represents the largest study to date to apply a comprehensive neuropsychological battery of tests to evaluate the cognitive functioning of children with MS, and the results clearly show us that cognitive issues are widespread and can occur early on in the disease course of these patients,” said Dr. Krupp, also a Professor of Neurology at Stony Brook University School of Medicine. “These are critically important findings that emphasize the need for prompt recognition of our patients’ cognitive problems and for neurologists and other MS specialists to discover ways to intervene and help improve the cognitive abilities of these children while they are in school and beyond.”
New drug target identified for multiple sclerosis and Alzheimer’s disease
Researchers at Boston University School of Medicine (BUSM) led by Carmela Abraham, PhD, professor of biochemistry, along with Cidi Chen, PhD, and other collaborators, report that the protein Klotho plays an important role in the health of myelin, the insulating material allowing for the rapid communication between nerve cells. These findings, which appear online in Journal of Neuroscience, may lead to new therapies for multiple sclerosis (MS) and Alzheimer’s disease (AD), in which white matter abnormalities are also common but have been largely ignored.
MS is an inflammatory disease which damages the fatty myelin sheaths around the axons of the brain and spinal cord. This destruction, loss or scarring of the sheaths results in a broad spectrum of symptoms. Disease onset usually occurs in young adults, most commonly women.
In MS the myelin is attacked by the immune system and may not be completely restored by myelin-producing cells (mature oligodendrocytes). The researchers discovered that the addition of Klotho protein to immature oligodendrocytes causes them to mature and manufacture proteins needed for the production of healthy myelin.
"These results taken together indicate that Klotho could become a drug target for multiple sclerosis and other white matter diseases, including AD," explained Abraham.
Abraham and her colleagues have identified, and are working on optimizing, a number of small molecules that could form the basis for the development of therapeutic drugs, which would increase the amount of Klotho protein in the brain.
Since Klotho is not only an age suppressor but also a tumor suppressor, as shown by other research groups, interventions with Klotho-enhancing drugs may solve some of the most treatment-resistant human ailments according to Abraham.
Klotho was named after the Greek Goddess and daughter of Zeus, who spins the thread of life. Abraham’s lab was the first to publish (in 2008) that Klotho levels in the brain decrease with age.
(Source)
Androgenic hormones could help treat multiple sclerosis
Testosterone and its derivatives could constitute an efficient treatment against myelin diseases such as multiple sclerosis, reveals a study by researchers from the Laboratoire d’Imagerie et de Neurosciences Cognitives (CNRS/Université de Strasbourg), in collaboration in particular with the “Neuroprotection et Neurorégénération: Molécules Neuroactives de Petite Taille” unit (Inserm/Université Paris-Sud). Myelin composes the sheaths that protect the nerve fibers and allow the speed of nerve impulses to be increased. A deficit in the production of myelin or its destruction cause serious illnesses for which there is no curative treatment. The researchers have shown that in mice brains whose nerve fibers have been demyelinated, testosterone and a synthetic analog induce the regeneration of oligodendrocytes, the cells responsible for myelination, and that they stimulate remyelination. This work is published on January in the journal Brain.
(Source)
Multiple sclerosis study reveals how killer T cells learn to recognize nerve fiber insulators
A micrograph of a killer T cell, a white blood cell that destroys germs or cancers, but that can sometimes attack the body’s own normal cells.
Misguided killer T cells may be the missing link in sustained tissue damage in the brains and spines of people with multiple sclerosis, findings from the University of Washington reveal. Cytoxic T cells, also known as CD8+ T cells, are white blood cells that normally are in the body’s arsenal to fight disease.
Multiple sclerosis is characterized by inflamed lesions that damage the insulation surrounding nerve fibers and destroy the axons, electrical impulse conductors that look like long, branching projections. Affected nerves fail to transmit signals effectively.
Intriguingly, the UW study, published this week in Nature Immunology, also raises the possibility that misdirected killer T cells might at other times act protectively and not add to lesion formation. Instead they might retaliate against the cells that tried to make them mistake the wrappings around nerve endings as dangerous.
Scientists Qingyong Ji and Luca Castelli performed the research with Joan Goverman, UW professor and chair of immunology. Goverman is noted for her work on the cells involved in autoimmune disorders of the central nervous system and on laboratory models of multiple sclerosis.
Multiple sclerosis generally first appears between ages 20 to 40. It is believed to stem from corruption of the body’s normal defense against pathogens, so that it now attacks itself. For reasons not yet known, the immune system, which wards off cancer and infection, is provoked to vandalize the myelin sheath around nerve cells. The myelin sheath resembles the coating on an electrical wire. When it frays, nerve impulses are impaired.
Depending on which nerves are harmed, vision problems, an inability to walk, or other debilitating symptoms may arise. Sometimes the lesions heal partially or temporarily, leading to a see-saw of remissions and flare ups. In other cases, nerve damage is unrelenting.
The myelin sheaths on nerve cell projections are fashioned by support cells called oligodendrocytes. Newborn’s brains contain just a few sections with myelinated nerve cells. An adult’s brains cells are not fully myelinated until age 25 to 30.
For T cells to recognize proteins from a pathogen, a myelin sheath or any source, other cells must break the desired proteins into small pieces, called peptides, and then present the peptides in a specific molecular package to the T cells. Scientists had previously determined which cells present pieces of a myelin protein to a type of T cell involved in the pathology of multiple sclerosis called a CD4+ T cell. Before the current study, no cells had yet been found that present myelin protein to CD8+ T cells.
Scientists strongly suspect that CD8+ T cells, whose job is to kill other cells, play an important role in the myelin-damage of multiple sclerosis. In experimental autoimmune encephalitis, which is a mouse model of multiple sclerosis in humans, CD4+ T cells have a significant part in the inflammatory response. However, scientists observed that, in acute and chronic multiple sclerosis lesions, CD8+T cells actually outnumber CD4+ T cells and their numbers correlate with the extent of damage to nerve cell projections. Other studies suggest the opposite: that CD8+ T cells may tone down the myelin attack.
The differing observations pointed to a conflicting role for CD8+ T cells in exacerbating or ameliorating episodes of multiple sclerosis. Still, how CD8+ T cells actually contributed to regulating the autoimmune response in the central nervous system, for better or worse, was poorly understood.
TIP dendritic cells, stained to show their physical features.
Goverman and her team showed for the first time that naive CD8+ T cells were activated and turned into myelin-recognizing cells by special cells called Tip-dendritic cells. These cells are derived from a type of inflammatory white blood cell that accumulates in the brain and the spinal cord during experimental autoimmune encephalitis originally mediated by CD4+ T cells. The membrane folds and protrusions of mature dendritic cells often look like branched tentacles or cupped petals well-suited to probing the surroundings.
The researchers proposed that the Tip dendritic cells can not only engulf myelin debris or dead oligodendrocytes and then present myelin peptides to CD4+ T cells, they also have the unusual ability to load a myelin peptide onto a specific type of molecule that also presents it to CD8+ T cells. In this way, the Tip dendritic cells can spread the immune response from CD4+ T cells to CD8+ T cells. This presentation enables CD8+ T cells to recognize myelin protein segments from oligodendrocytes, the cells that form the myelin sheath. The phenomenon establishes a second-wave of autoimmune reactivity in which the CD8+ T cells respond to the presence of oligodendrocytes by splitting them open and spilling their contents.
“Our findings are consistent,” the researchers said, “with the critical role of dendritic cells in promoting inflammation in autoimmune diseases of the central nervous system.” They mentioned that mature dendritic cells might possibly wait in the blood vessels of normal brain tissue to activate T-cells that have infiltrated the blood/brain barrier.
The oligodendrocytes, under the inflammatory situation of experimental autoimmune encephalitis, also present peptides that elicit an immune response from CD8+ T cells. Under healthy conditions, oligodendrocytes wouldn’t do this.
The researchers proposed that myelin-specific CD8+ T cells might play a role in the ongoing destruction of nerve-cell endings in “slow burning” multiple sclerosis lesions. A drop in inflammation accompanied by an increased degeneration of axons (electrical impulse-conducting structures) coincides with multiple sclerosis leaving the relapsing-remitting stage of disease and entering a more progressive state.
Medical scientists are studying the roles of a variety of immune cells in multiple sclerosis in the hopes of discovering pathways that could be therapeutic targets to prevent or control the disease, or to find ways to harness the body’s own protective mechanisms. This could lead to highly specific treatments that might avoid the unpleasant or dangerous side effects of generalized immunosuppressants like corticosteroids or methotrexate.
(Source: washington.edu)
Simple eye scan can reveal extent of Multiple Sclerosis
A simple eye test may offer a fast and easy way to monitor patients with multiple sclerosis (MS), medical experts say in the journal Neurology. Optical Coherence Tomography (OCT) is a scan that measures the thickness of the lining at the back of the eye - the retina. It takes a few minutes per eye and can be performed in a doctor’s surgery.
In a trial involving 164 people with MS, those with thinning of their retina had earlier and more active MS. The team of researchers from the Johns Hopkins University School of Medicine say larger trials with a long follow up are needed to judge how useful the test might be in everyday practice. The latest study tracked the patients’ disease progression over a two-year period.
Unpredictable disease
Multiple sclerosis is an illness that affects the nerves in the brain and spinal cord causing problems with muscle movement, balance and vision. In MS, the protective sheath or layer around nerves, called myelin, comes under attack which, in turn, leaves the nerves open to damage.
There are different types of MS - most people with the condition have the relapsing remitting type where the symptoms come and go over days, weeks or months. Usually after a decade or so, half of patients with this type of MS will develop secondary progressive disease where the symptoms get gradually worse and there are no or very few periods of remission.
Another type of MS is primary progressive disease where symptoms get worse from the outset. There is no cure but treatments can help slow disease progression. It can be difficult for doctors to monitor MS because it has a varied course and can be unpredictable.
Brain scans can reveal inflammation and scarring, but it is not clear how early these changes might occur in the disease and whether they accurately reflect ongoing damage.
Scientists have been looking for additional ways to track MS, and believe OCT may be a contender. OCT measures the thickness of nerve fibres housed in the retina at the back of the eye. Unlike nerve cells in the rest of the brain which are covered with protective myelin, the nerve cells in the retina are bare with no myelin coat. Experts suspect that this means the nerves here will show the earliest signs of MS damage.
The study at Johns Hopkins found that people with MS relapses had much faster thinning of their retina than people with MS who had no relapses. So too did those whose level of disability worsened. Similarly, people with MS who had inflammatory lesions that were visible on brain scans also had faster retinal thinning than those without visible brain lesions. Study author Dr Peter Calabresi said OCT may show how fast MS is progressing.
"As more therapies are developed to slow the progression of MS, testing retinal thinning in the eyes may be helpful in evaluating how effective those therapies are," he added.
In an accompanying editorial in the same medical journal that the research is published in, MS experts Drs Robert Bermel and Matilde Inglese say OCT “holds promise” as an MS test.
(Image courtesy: Boston University Eye Associates, Inc.)
Gladstone Scientists Identify Key Biological Mechanism in Multiple Sclerosis
Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS)—a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.
Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.
(Source: gladstoneinstitutes.org)
Combination of two pharmaceuticals proves effective in the treatment of multiple sclerosis
A new substance class for the treatment of multiple sclerosis and other neurodegenerative diseases now promises increased efficacy paired with fewer side effects. To achieve this, a team of scientists under the leadership of Prof. Gunter Fischer (Max Planck Research Unit for Enzymology of Protein Folding, Halle/Saale, Germany) and Dr. Frank Striggow (German Center for Neurodegenerative Diseases (DZNE)) have combined two already approved pharmaceutical substances with each other using a chemical linker structure. The objectives of this combination are to ensure maximum brain cell protection on the one hand and the suppression of unwanted side effects on the other. The new class of substances has now been registered with the European Patent Office as the DZNE’s first patent in the form of a joint patent application with the Max Planck Research Unit. “The patent approval process can take several years. During this phase we are planning to conclude the pre-clinical development. It is our aim to start with clinical research and development at the earliest possible time. Overall, we have identified substantial therapeutic potential as far as chronic and age-related neurodegenerative diseases are concerned,” comments Dr. Frank Striggow.
Experimental Drug Improves Memory in Mice with Multiple Sclerosis
Johns Hopkins researchers report the successful use of a form of MRI to identify what appears to be a key biochemical marker for cognitive impairment in the brains of people with multiple sclerosis (MS). In follow-up experiments on mice with a rodent form of MS, researchers were able to use an experimental compound to manipulate that same marker and dramatically improve learning and memory.
Half of people with MS experience learning and memory problems, for which there is no approved treatment, along with movement abnormalities that characterize the debilitating autoimmune disorder.
"We have a potentially novel treatment for cognitive impairment in MS, a devastating condition on the rise that affects at least 400,000 people in the United States," says study leader Adam I. Kaplin, M.D., Ph.D., an assistant professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine.
Kaplin cautions that the treatment has so far been used only in mouse models of MS and is years away from clinical trials in people.
Nevertheless, he says, the research, described in the Proceedings of the National Academy of Sciences published online on Nov. 19, has the potential to speed development of new drugs to treat cognitive impairment not only in MS patients, but also in patients with Alzheimer’s disease and other neurological conditions.
Breakthrough nanoparticle halts multiple sclerosis
In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research.
The new nanotechnology also can be applied to a variety of immune-mediated diseases including Type 1 diabetes, food allergies and airway allergies such as asthma.
In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can’t be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.
The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.
"This is a highly significant breakthrough in translational immunotherapy," said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. "The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that’s delivered."
"The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin," Miller added. "Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact."
The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and Applied Science.
"This is a major breakthrough in nanotechnology, showing you can use it to regulate the immune system," said Shea, also a corresponding author. The paper was published Nov. 18 in the journal Nature Biotechnology.