Category: Multiple Sclerosis

A national conversation continues about the best ways to improve both the quality of medical care and to contain costs. So far, developing quality measurements has focused on primary care or highly prevalent, chronic conditions such as asthma and diabetes. But what about brain disorders? To date, the number of measures that apply to neurologic care has been limited.

The American Academy of Neurology (AAN), an association of more than 22,500 neurologists and neuroscience professionals, reached out to a group of neurologists to develop such a set of measurements. Led by Dr. Eric M. Cheng, a UCLA assistant professor of neurology, the group developed a new tool to help doctors gauge how well they are caring for people with Parkinson's disease, a neurological disorder that is estimated to effect nearly 1 million people in the United States. The results are published in Neurology, the medical journal of the AAN.

"Measuring the quality of health care is a fundamental step toward improving it," said Cheng, lead author of the study and a clinician with the Veterans Administration Greater Los Angeles Healthcare System. "Quality measures have been developed for conditions seen by primary care doctors for years, but not for many specialty care conditions such as brain disorders."

The AAN has developed measures for stroke and epilepsy and is working on developing similar measures for dementia, neuropathy and multiple sclerosis. The measures for Parkinson's are intended to help doctors determine how well they care for their patients. The group developed 10 separate measures to evaluate care for Parkinson's patients, including non-motor (movement) symptoms, such as depression or sleep, which are strongly associated with quality of life. Another measures the patient's current diagnosis or treatment, while another measures safety, including counseling on preventable complications, such as falls.

"Quality measures like these will be increasingly important for extending the best care possible to people with neurologic disorders like Parkinson's," said Cheng. "But none of these measures prescribe the use of specific medications, assessment tools or treatment options. It was important to leave clinicians with flexibility in how the measures can be successfully completed."

The study was funded by the AAN. Besides Cheng, five other authors were involved with the study. Cheng is supported by the VA Parkinson's Disease Research, Education and Clinical Center. He is also involved with the National Parkinson Foundation and receives research support from the National Institutes of Health, Department of Veterans Affairs, National Multiple Sclerosis Society and the American Heart Association.

By tracking the fate of a group of immature cells that persist in the adult brain and spinal cord, Johns Hopkins researchers discovered in mice that these cells undergo dramatic changes in amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.

A study reported November 17 online in Neuron shows that these cells, called NG2+, grow and expand rapidly during early life, eventually morphing into mature nervous system cells called oligodendrocytes. These "oligos" help speed the transmission of electrical impulses by providing insulation around nerve cells. This insulation, known as myelin, is disrupted in nervous system diseases such as multiple sclerosis.

The team tracked the fate of NG2+ cells in both normal mice and mice with a mutant form of the SOD1 gene that causes ALS. Using a stringent system that let them color-tag only NG2+ cells and then accurately locate these cells at various times in their development, the researchers found that NG2+ cells normally keep up a quiet program of dividing in adult tissues, sometimes replacing themselves and other times forming new oligos.

A slow and steady turnover of oligodendrocytes may be required throughout life to maintain myelin, says Dwight Bergles, Ph.D., associate professor in The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine. However, the normal developmental program of NG2+ cells goes awry in the spinal cords of ALS mice.

"In the model ALS mice we studied, it's as though NG2+ cells step onto a high-speed treadmill," Bergles says. "They undergo explosive division, morph more readily into abnormal-looking oligodendrocytes and then, uncharacteristically, those differentiated cells quickly die. The brakes that normally hold these cells in check appear to be gone in ALS."

Of special note are provocative data showing this cell type as the most proliferating cell population in the spinal cords of ALS mice, churning out even more oligodendrocytes than in normal mice, says Shin Kang, Ph.D, a research associate in The Solomon H. Snyder Department of Neuroscience.

"This suggests there is significant oligodendrocyte death even before anything else degenerates," he explains, "which identifies a new and important player in the progression of this disease."

All this frenetic oligodendrocyte-generating activity takes place in the central nervous system's gray matter where other cells — the motor neurons — are dying. A body of research shows that after acute trauma to the central nervous system, a short-term upswing in NG2+ activity takes place that may help reduce the extent of damage. Whether this change in behavior of NG2+ cells is protective, or accelerates the death of motor neurons in ALS, is not yet known.

Earlier studies in lab-dish cultures showed that NG2+ cells acted like stem cells, capable of turning into the major cell types in the nervous system, suggesting that they could be harnessed to replace cells that died as a result of injury or disease. However, the Hopkins team saw no evidence that the cells become anything other than oligodendrocytes in both healthy animals and those carrying the ALS mutant gene.

"Although we found that the potential of these cells is more limited than previously thought, it might be possible to coax them to adopt different fates," Bergles says. "We only need to know what factors are restricting their development in the intact nervous system."

"This goes much further than simply confirming a negative finding about these mysterious cells," adds Kang. "We've answered a question, but the new observation about the overgrowth could lead to an entirely new understanding of ALS."

The study was supported by the Packard Center for ALS Research at Johns Hopkins and its sister organization, P2ALS, and by grants from the National Institutes of Health and Muscular Dystrophy Association.

Johns Hopkins authors of the study, in addition to Bergles, are Shin H. Kang, Jason K. Yang, and Jeffrey D. Rothstein. Masahiro Fukaya, Hokkaido University Graduate School of Medicine, Sapporo, Japan, is also an author.

Journal Reference:

1. Shin H. Kang, Masahiro Fukaya, Jason K. Yang, Jeffrey D. Rothstein, Dwight E. Bergles. NG2 CNS Glial Progenitors Remain Committed to the Oligodendrocyte Lineage in Postnatal Life and following Neurodegeneration. Neuron, Volume 68, Issue 4, 668-681, 18 November 2010 DOI: 10.1016/j.neuron.2010.09.009

 Individuals with the autoimmune skin disease bullous pemphigoid appear more likely to have a diagnosis of neurologic disease, such as dementia and cerebrovascular disease, according to a report in the November issue of Archives of Dermatology, one of the JAMA/Archives journals.

"Bullous pemphigoid is a debilitating autoimmune skin disease that is characterized by large, tense blisters on the skin of the elderly," the authors write as background information in the article. The condition affects about 43 per million individuals per year in the United Kingdom and 7 to 13 per million in other parts of Europe. "Over the last two decades, various neurologic diseases have been described in association with bullous pemphigoid, including cerebrovascular disease, dementia, multiple sclerosis, epilepsy, Parkinson disease, Shy-Drager syndrome and amyotrophic lateral sclerosis."

Kathy Taghipour, M.D., M.R.C.P., of Oxford Radcliffe Hospitals, Oxford, England, and colleagues assessed 90 consecutive patients with bullous pemphigoid and 141 controls without the condition. Medical histories were reviewed for the presence of neurologic disease, defined as a confirmed diagnosis by a hospital physician; positive imaging findings; or considerable functional disability due to mental impairment.

Among patients with bullous pemphigoid, 42 (46 percent) had at least one neurologic disease, compared with 16 controls (11 percent). Four major neurologic diseases were observed among these patients: cerebrovascular disease, dementia, Parkinson's disease and epilepsy. However, only rates of cerebrovascular disease and dementia were significantly greater among patients than among controls.

Of the 36 patients with accurate information about the timing of their diagnoses, bullous pemphigoid was diagnosed after neurologic disease in most (26 of 36 or 72 percent), with a median (midpoint) time of 5.5 years between diagnoses.

"Neurologic symptoms may often be subtle, and the onset of disease may be insidious, leading to diagnostic delay," the authors write. "It is therefore likely that the interval between neurologic disease and bullous pemphigoid is longer than estimated, and it is tempting to speculate that certain neurologic conditions can predispose to bullous pemphigoid." The association could be explained by an immunologic cross-reactivity between the skin and the brain, in which neurologic disorders trigger an immune response that affects the skin, the authors note.

"The relationship between bullous pemphigoid and neurologic disease has been the subject of numerous case reports, but epidemiological data are scarce, and this subgroup of patients with bullous pemphigoid have not been further characterized," they conclude. "We have demonstrated that there is a significant association between bullous pemphigoid and neurologic disorders, in particular cerebrovascular disease and dementia, and that neurologic disease may be a predisposing factor for bullous pemphigoid. The mechanism by which neurologic disease may trigger bullous pemphigoid remains obscure and requires further investigation."

Journal Reference:

1. Kathy Taghipour; Ching-Chi Chi; Angela Vincent; Richard W. Groves; Vanessa Venning; Fenella Wojnarowska. The Association of Bullous Pemphigoid With Cerebrovascular Disease and Dementia: A Case-Control Study. Archives of Dermatology, 2010; 146 (11): 1251-1254 DOI: 10.1001/archdermatol.2010.322

 It's known that the development of neuronal diseases such as multiple sclerosis and Alzheimer's disease is connected with the levels of myelin — an insulating substance around nerve fibres — in the body, although the actual causes of these conditions remain unknown. Now researchers at IBEC have discovered a new group of interacting partners for myelin-associated receptors, which could shed light on the significance of imbalanced production or modifications of the substance.

In a study published online by The FASEB Journal this week, group leader José Antonio del Río, together with his postdocs Vanessa Gil and Franc Llorens, have been looking at axons, ligands and receptors in the mammalian central nervous system. Following injury in adults, axons have a limited capacity for regrowth; this restriction is caused by myelin-associated inhibitors (MAIs).

A release from myelin inhibition thus improves neuronal regeneration, and the three researchers from IBEC's Molecular and Cellular Neurobiotechnology group have discovered that blocking two of some of these proteins' shared receptors — NgR1, together with its coreceptors p75(NTR), TROY and Lingo-1, and paired immunoglobulin-like receptor B (PirB) — prevents the inhibitors from restricting axonal sprouting and limiting the regeneration of damaged fibre tracts.

Other elements of the myelin inhibitory pathway are still unknown, but this identification and characterization of the roles and functions of some of the inhibitory molecules sheds light on one of the most competitive areas of research into neuroregeneration of the past several years. In addition, further data from within and outside the CNS environment suggests that most of these proteins have other roles beyond axonal growth inhibition.

"Potentially there could be new physiological roles for them in other processes such as development, neuronal homeostasis, plasticity and neurodegeneration," says José Antonio. "Modifications could be considered as markers for certain neuronal diseases."

Journal Reference:

1. Llorens, F., Gil, V., del Río, J. A. Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration. FASEB J., 2010 Nov 8 [link]

NewsPsychology (Nov. 9, 2010) — A small study suggests women with multiple sclerosis have lower vitamin D levels during pregnancy and breastfeeding, according to a report posted online that will appear in the March 2011 print issue of Archives of Neurology, one of the JAMA/Archives journals. However, these vitamin D levels were not associated with a greater risk of multiple sclerosis relapse after childbirth.

“During the last decade, low level of vitamin D, a potent immunomodulator, has emerged as an important risk factor for multiple sclerosis (MS) as well as other autoimmune diseases and certain cancers,” the authors write as background information in the article. “The observation that healthy pregnant and lactating women are at particularly high risk of vitamin D insufficiency, regardless of race, suggests that pregnant and nursing mothers with MS may have a higher risk of relapses. However, it has already been well established that the risk of MS relapse decreases during pregnancy and increases in the postpartum period and that breastfeeding does not increase the risk of relapses.”

Annette Langer-Gould, M.D., Ph.D., then of Stanford University School of Medicine, Stanford, Calif., and now of Kaiser Permanente Southern California’s Department of Research and Evaluation, Pasadena, and colleagues studied 28 pregnant women with MS from Kaiser Permanente Northern California and the Stanford University outpatient neurology clinics. Participants donated blood and completed questionnaires at the beginning of the study, during their remaining trimesters of pregnancy and regularly during the first year after birth.

Of the 28 women, half (14) breastfed exclusively and 43 percent (12) relapsed within six months after giving birth. During pregnancy, average blood levels of 25-hydroxyvitamin (25[OH]D, a common measure of vitamin D) were 25.4 nanograms per milliliter, and were associated with the season. After birth, levels remained low among women who were exclusively breastfeeding. By four and six months after childbirth, 25(OH)D levels were an average of 5 nanograms per milliliter lower among women who breastfed exclusively than among women who did not.

However, these low postpartum vitamin D levels were not associated with risk of MS relapse. “If anything, by three to six months after childbirth, 25(OH)D levels were marginally higher among the women who relapsed within the first six months after childbirth compared with women who were relapse-free during the corresponding period,” the authors write. “We do not believe that higher vitamin D levels increase the risk of postpartum relapses, as the rise we observed did not appear to occur prior to the onset of symptoms and the findings were of marginal statistical significance after accounting for season. Instead, we think this apparent inverse association is a reflection of the fact that most of the women who relapsed in the study also did not breastfeed or did so only briefly.”

The findings imply that the recommended dose of vitamin D supplementation for women with MS during pregnancy and breastfeeding should be the same as for women who do not have MS, the authors conclude. “Our results suggest that future studies aimed at identifying and unraveling the relationship between vitamin D, pregnancy/lactation-related hormones and regulation of MS inflammation may reveal novel insights into MS pathophysiology,” they write.

Email or share this story:

Story Source:

The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by JAMA and Archives Journals.

Journal Reference:

1. Annette Langer-Gould; Stella Huang; Stephen K. Van Den Eeden; Rohit Gupta; Amethyst D. Leimpeter; Kathleen B. Albers; Ron Horst; Bruce Hollis; Lawrence Steinman; Lorene M. Nelson. Vitamin D, Pregnancy, Breastfeeding, and Postpartum Multiple Sclerosis Relapses. Arch Neurol, 2010; 0 (2010): archneurol. 2010. 291 DOI: 10.1001/archneurol.2010.291

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

Statins, the family of drugs used to lower cholesterol, might also reduce the risk of epileptic seizures in people with cardiovascular disease, according to a new statistical study by a drug safety expert at the University of British Columbia and Vancouver Coastal Health Research Institute. The findings could provide the basis for randomized, controlled clinical trials to test the efficacy of the drugs as anti-epileptic medication.

The study, based on a database of 2,400 Quebec residents aged 65 and older, showed that those taking statins were 35 per cent less likely to be hospitalized with a diagnosis of epilepsy than those not taking the drug. The data was culled from a larger database containing detailed information on 150,000 cardiovascular patients in Quebec.

Published in the journal Neurology, the study does not prove causation but only reveals an association between use of statins and the incidence of epilepsy. Such "observational" studies are crucial to generating hypotheses about drugs, providing a basis for clinical trials.

Epilepsy, which affects 50 million people worldwide, is a brain disorder in which clusters of brain cells sometimes signal abnormally, causing strange sensations, emotions, and behavior or sometimes convulsions, muscle spasms, and loss of consciousness. It's estimated that 30 per cent of epilepsy patients continue having seizures despite receiving the standard drug therapy.

This is the first large study involving humans to show a correlation between statins, the most prescribed class of cardiovascular medications, and seizures, which may be life-threatening. One statin drug, atorvastatin (sold under the trade name Lipitor), has been shown to decrease seizures and neuron death in rats. Statins also have shown protective effects in other neurological disorders, including multiple sclerosis and spinal cord injury.

"Our data is compelling in that it opens doors for future studies to test this hypothesis in patients with epilepsy," says Dr. Mahyar Etminan, a pharmacoepidemiologist and lead author of the article. Etminan is a scientist and clinical pharmacist at the Centre for Clinical Epidemiology at Vancouver Coastal Health Research Institute and an assistant professor in the Dept. of Medicine at UBC. "Such trials would show whether statins truly have a protective effect, and if that effect is limited to certain types of statins or certain types of epilepsy."

"Our study suggests that statin use reduces the risk of developing epilepsy in persons over the age of 65 with cardiovascular disease," says Dr. Ali Samii, a professor in the Department of Neurology at the University of Washington, and co-author of the article. "The most plausible explanation is that statin use reduces the risk of stroke in this population, and since strokes can increase the risk of epilepsy, statins reduce the risk of epilepsy because of stroke prevention."

But Samii notes that other classes of cardiovascular drugs, such as beta-blockers and ACE inhibitors, also reduce the risk of stroke, and yet they did not show the same effect. Therefore, statins may reduce the risk of epilepsy in this patient population by mechanisms other than just stroke prevention.

Co-author Dr. James M. Brophy, of the McGill University Dept. of Medicine, provided the database used for the study. The research was supported by the Vancouver Coastal Health Research Institute.

Journal Reference:

1. Mahyar Etminan, Ali Samii, and James M. Brophy. Statin use and risk of epilepsy: A nested case-control study. Neurology, 2010; 75: 1496-1500

Stereotactic radiation is an effective, long-term treatment for trigeminal neuralgia: a painful condition that occurs with increased frequency in patients with multiple sclerosis (MS). Radiation is noninvasive and has less negative side effects than other treatments, according to the longest follow-up in a study of its kind to be presented Oct. 31, 2010, at the 52nd Annual Meeting of the American Society for Radiation Oncology (ASTRO).

Multiple sclerosis is a progressive neurological disease affecting about 300,000 Americans where the body's immune system attacks its own nerve cells, affecting the ability of the brain to communicate with the spinal cord. Trigeminal neuralgia is an intensely painful condition caused by dysfunction of the trigeminal nerve, which is one of the nerves that innervates the face. People living with MS see a significantly increased incidence of this problem.

"We studied patients for a median of five years after treatment, which is the longest period of follow-up ever completed," Tejan Diwanji, lead author of the study at the University of Maryland, School of Medicine in Baltimore, said "Our study shows that radiosurgery using Gamma Knife is a proven alternative to surgery or anti-epileptic drugs."

The study was designed to determine the long-term effectiveness of treating trigeminal neuralgia in MS patients with Gamma Knife radiosurgery.

Stereotactic radiation is a specialized type of external beam radiation therapy that uses focused radiation beams to target a well-defined area. It is most often used for tumors of the brain, but in this case, doctors targeted a nerve root, relying on detailed imaging and computerized three-dimensional planning to deliver the radiation dose with extreme accuracy while sparing the surrounding tissue to reduce side effects.

Stereotactic radiation therapy, sometimes called radiosurgery, refers to a single or several treatments to the brain. Doctors in this study used GammaKnife. Other brand names for stereotactic radiation include Axesse, CyberKnife, Novalis, Primatom, Synergy, X-Knife, TomoTherapy or Trilogy.

The study involved 13 MS patients with trigeminal neuralgia who were treated with radiosurgery at the University of Maryland between 1998 and 2001 and were followed for a median of five years after treatment.

"We need more long-term studies to confirm the positive and lasting outcomes of radiosurgery, then it could become the treatment of choice for MS patients afflicted with trigeminal neuralgia," Diwanji, said. "I encourage people with MS suffering from trigeminal neuralgia to talk to their doctor about consulting a radiation oncologist to see if they would be good candidates for radiosurgery."

Researchers in Germany have gained new insight into how the immune system causes damage associated with multiple sclerosis (MS), an incurable neuroinflammatory disorder. Using imaging tools which enable investigation of processes in living organisms, they were able to show a direct interaction between immune cells and neurons which plays a significant role in neuronal injury. However, this direct interaction may respond to therapeutic intervention.

The study by Dr. Volker Siffrin and Professor Dr. Frauke Zipp (formerly Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch, now University Medical Center Johannes Gutenberg University, Mainz) has now been published in the journal Immunity.

Multiple sclerosis is an autoimmune disease in which a person's own immune system attacks the central nervous system. Symptoms of the disease are variable depending on which nerves are affected, but often include muscle weakness, walking difficulties, numbness and visual disturbances. Research has shown that MS is caused by damage to the protective myelin sheath, an insulating substance that surrounds nerve processes and is critical for transmission of nerve impulses.

Research has also indicated that direct damage to neurons is prominent in early disease stages. "The contribution of direct neuronal damage to MS pathology has been debated since the first description of the disease," explained Professor Frauke Zipp, senior author of the study. "Although many different theories about possible underlying mechanisms have been proposed — such as neuron damage being a secondary effect of the disrupted myelin sheath — actual events leading to neural damage are not well understood."

To investigate processes in the living organisms, Dr. Zipp and her colleagues used two-photon laser scanning microscopy (TPLSM), with which they studied the role immune cells play in neuronal damage in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. They observed direct synapse-like interactions between immune cells and neurons.

Immune cells called Th17 cells, which have been linked to autoimmune inflammation, induced elevated calcium levels in the neurons, which in the long run are toxic to the cells. Normally, calcium within the neuron plays a crucial role in exciting nerve cells as well as muscle cells.

This is significant because fluctuations in neuronal intracellular calcium levels that are linked to cell injury are partially reversible when the researchers expose the lesions of the animals to compounds used to treat excitotoxicity.

These results highlight a specific interaction between the immune system and the nervous system, implicating direct neuronal damage in autoimmune-mediated inflammation. "Our use of in vivo imaging during disease has led to the characterization of neuronal dysfunction as early and potentially reversible, and suggests that immune-mediated disturbances of the neurons themselves contribute to multiple sclerosis, in addition to interruptions in nerve cell transmission as a result of changes to the myelin sheath," Professor Zipp concluded.

"Furthermore, immune-mediated reversible calcium increases in neurons are a potential target for future therapeutics." However, it will take many years to find out if this is a strategy which will work for treating MS.

Journal Reference:

1. Volker Siffrin, Helena Radbruch, Robert Glumm, Raluca Niesner, Magdalena Paterka, Josephine Herz, Tina Leuenberger, Sabrina M. Lehmann, Sarah Luenstedt, Jan Leo Rinnenthal, Gregor Laube, Hervé Luche, Seija Lehnardt, Hans-Joerg Fehling, Oliver Griesbeck, Frauke Zipp. In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis. Immunity, 2010; DOI: 10.1016/j.immuni.2010.08.018

Adding albuterol, a compound commonly used to treat asthma and other respiratory diseases, to an existing treatment for patients with multiple sclerosis appears to improve clinical outcomes, according to a report in the September issue of Archives of Neurology, one of the JAMA/Archives journals.

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by the degeneration of myelin, which coats nerve cells in the white matter of the central nervous system. Patients with the condition have been found to have elevated levels of interleukin-12, a biological compound that promotes the generation of a type of helper T cell that may be associated with myelin destruction.

Albuterol sulfate — commonly used to treat bronchospasm, a constriction of the airways within the lungs as often occurs in asthma — may decrease interleukin-12 levels, the authors note. Samia J. Khoury, M.D., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues assessed the effects of albuterol treatment as an add-on therapy for patients starting treatment with glatiramer acetate, currently approved as a therapy for relapsing-remitting MS.

A total of 44 patients were randomly assigned to receive daily subcutaneous (underneath the skin) 20-milligram injections of glatiramer acetate plus either an oral dose of 4 milligrams of albuterol or placebo daily for two years. Participants were examined by a neurologist at the beginning of the study and at six, 12, 18 and 24 months, and blood samples were collected at the beginning and three, six and 12 months into the study. Magnetic resonance imaging (MRI) of the brain was performed at enrollment, 12 months and 24 months.

A total of 39 patients participated long enough to contribute to the analysis. In assessments of functional status, improvement was observed in the glatiramer acetate plus albuterol group compared with the placebo group at six months and 12 months but not at 24 months. Compared to patients taking placebo, those taking albuterol also experienced a delay in the time to their first relapse.

Blood tests showed that the production of two inflammatory markers — interleukin-13 and interferon-gamma — decreased in both treatment groups, with a treatment effect on interleukin-13 observed at the 12-month time point.

Adverse events were generally mild, with only three moderate or severe events that were considered to be related to the treatment (including reaction at the glatiramer acetate injection site, leg weakness and chest tightness).

"We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis," the authors write. "The combined regimen seems to enhance clinical response during the first year of therapy."

Journal Reference:

1. Samia J. Khoury; Brian C. Healy; Pia Kivisakk; Vissia Viglietta; Svetlana Egorova; Charles R. G. Guttmann; Josiah F. Wedgwood; David A. Hafler; Howard L. Weiner; Guy Buckle; Sandra Cook; Susheel Reddy. A Randomized Controlled Double-Masked Trial of Albuterol Add-on Therapy in Patients With Multiple Sclerosis. Arch Neurol, 2010; 67 (9): 1055-1061 [link]

Vanishing White Matter (VWM) disease is a devastating condition that involves the destruction of brain myelin due to a mutation in a central factor. To understand the disease and test potential treatments that could apply to other disorders, such as multiple sclerosis, Prof. Orna Elroy-Stein of Tel Aviv University's Department of Cell Research and Immunology is leading a scientific breakthrough by developing laboratory mice which carry the VWM mutation — an important new tool.

The mice harbor a mutation of the eIF2B enzyme, which regulates protein synthesis in every cell throughout the body. The key to the new development, says Prof. Elroy-Stein, was the use of genetically-engineered embryonic stem cells to introduce the mutation.

The brain is made up of two components: grey matter, or nerves, and white matter, or glial cells which support the nerves and produce myelin, which wraps around and protects nerve extensions. Recently described in the journal Brain, the creation of these mutated mice allows for new research on VWM diseases, which trigger loss of myelin in the brain, leading to paralysis and possible death.

A new breed of mouse and man

Until now, VWM researchers did not have a comparable animal model with which to study the disease. Now, for the first time, researchers can use a living organism to follow the exact process of myelin destruction, providing valuable information about the molecular mechanisms of the disease, which are currently unknown.

The big surprise in this discovery, she says, is that the gene mutation impacts only the white matter of the brain, rather than causing disease throughout the body. This will allow researchers to learn about myelin formation and maintenance.

"For the first time ever, we can follow the regulated expression of the protein components of myelin," explains Prof. Elroy-Stein, whose techniques include magnetic resonance imaging to investigate what's happening in the brains of the mice.

Not only will this discovery lead to a greater understanding of diseases that affect the brain's white matter, the mice are also an invaluable testing ground for new treatments. But according to Prof. Elroy-Stein, understanding the disease is the first step. "In order to develop effective therapies, one has to understand the mechanisms," she says.

Prof. Elroy-Stein notes that this is an entirely TAU-led project. The team of researchers include her Ph.D. students Michal Geva, Yuval Cabilly, Liraz Marom, Nina Mindroul, and Gali Raini; lab technician Dalia Pinchasi; and Dr. Yaniv Assaf of Tel Aviv University's Department of Neurobiology.