Category: Multiple Sclerosis

Scientists from the Florida campus of The Scripps Research Institute have developed the first of a new class of highly selective compounds that effectively suppresses the severity of multiple sclerosis in animal models. The new compound could provide new and potentially more effective therapeutic approaches to multiple sclerosis and other autoimmune diseases that affect patients worldwide.

The study appeared April 17, 2011, in an advance online edition of the journal Nature.

Current treatments for autoimmunity suppress the patient's entire immune system, leaving patients vulnerable to a range of adverse side effects. Because the new compound, known as SR1001, only blocks the actions of a specific cell type playing a significant role in autoimmunity, it appears to avoid many of the widespread side effects of current therapies.

"This is a novel drug that works effectively in animal models with few side effects," said Tom Burris, Ph.D., a professor in the Department of Molecular Therapeutics at Scripps Florida who led the study, which was a multidisciplinary collaboration with scientists including Patrick Griffin, William Roush, and Ted Kamenecka of Scripps Research, and Paul Drew of the University of Arkansas for Medical Sciences. "We have been involved in several discussions with both pharmaceutical and biotechnology firms who are very interested in developing it further."

A lengthy process of drug development and review is required to ensure a new drug's safety and efficacy before it can be brought to market.

"This impressive multidisciplinary team has used a combined structural and functional approach to describe a class of molecules that could lead to new medicines for treating autoimmune diseases," said Charles Edmonds, Ph.D. who oversees structural biology grants at the National Institutes of Health. "Breakthroughs such as this highlight the value of scientists with diverse expertise joining forces to solve important biological problems that have the potential to benefit human health."

Targeting Specific Receptors

For the past several years, Burris and his colleagues have been investigating small-molecule compounds that affect particular disease-related receptors (structures that bind other molecules, triggering some effect on the cell). In particular, the scientists have been interested in a pair of "orphan nuclear receptors" (receptors with no known natural binding partner) called RORα and RORγ involved in both autoimmune and metabolic diseases.

These particular receptors play a critical role in the development of TH17 cells, a form of T helper cells that make up part of the immune system. A relatively new discovery, TH17 cells have been implicated in the pathology of numerous autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and lupus. TH17 cells produce Interleukin-17, a natural molecule that can induce inflammation, a characteristic of autoimmunity.

"If you eliminate TH17 cell signals, you basically eliminate the disease in animal models," Burris said. "Our compound is the first small-molecule orally active drug that targets this specific cell type and shuts it down. Once SR1001 is optimized, chances are it will be far more potent and effective."

The compound works without affecting other types of T helper cells and without any significant metabolic impact, Burris added.

The first author of the study is Laura A. Solt of Scripps Research. In addition to Burris, Griffin, Roush, Kamenecka, Drew, and Solt, other authors include Naresh Kumar, Philippe Nuhant, Yongjun Wang, Janelle L. Lauer, Jin Liu, and Monica Istrate of Scripps Research; Dušica Vidović, Stephan C. Schürer of Scripps Research and the Center for Computational Science, University of Miami; and Jihong Xu and Gail Wagoner of the University of Arkansas for Medical Sciences.

The study was supported by the National Institutes of Health's National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute of Mental Health.

Journal Reference:

1. Laura A. Solt, Naresh Kumar, Philippe Nuhant, Yongjun Wang, Janelle L. Lauer, Jin Liu, Monica A. Istrate, Theodore M. Kamenecka, William R. Roush, Dušica Vidović, Stephan C. Schürer, Jihong Xu, Gail Wagoner, Paul D. Drew, Patrick R. Griffin, Thomas P. Burris. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature, 2011; DOI: 10.1038/nature10075

Patients with a recent onset of Parkinson disease have a high prevalence of vitamin D insufficiency, but vitamin D concentrations do not appear to decline during the progression of the disease, according to a report in the March issue of Archives of Neurology, one of the JAMA/Archives journals.

Vitamin D is now considered a hormone that regulates a number of physiological processes. "Vitamin D insufficiency has been associated with a variety of clinical disorders and chronic diseases, including impaired balance, decreased muscle strength, mood and cognitive dysfunction, autoimmune disorders such as multiple sclerosis and diabetes (types 1 and 2), and certain forms of cancer," the authors write as background information in the article. "Vitamin D insufficiency has been reported to be more common in patients with Parkinson disease (PD) than in healthy control subjects, but it is not clear whether having a chronic disease causing reduced mobility contributes to this relatively high prevalence."

Marian L. Evatt, M.D., M.S., of Emory University School of Medicine and the Atlanta Veterans Affairs Medical Center, and colleagues examined the prevalence of vitamin D insufficiency in untreated patients with early PD, diagnosed within five years of entry into the study. They conducted a survey study of vitamin D status in stored blood samples from patients with PD who were enrolled in the placebo group of the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial.

The authors found a high prevalence of vitamin D insufficiency and deficiency in 157 study participants with early, untreated PD. At the baseline visit, most study participants (69.4 percent) had vitamin D insufficiency and more than a quarter (26.1 percent) had vitamin D deficiency. "At the end point/final visit, these percentages fell to 51.6 percent and 7 percent, respectively."

"Contrary to our expectation that vitamin D levels might decrease over time because of disease-related inactivity and reduced sun exposure, vitamin D levels increased over the study period," the authors write. "These findings are consistent with the possibility that long-term insufficiency is present before the clinical manifestations of PD and may play a role in the pathogenesis of PD."

Vitamin D insufficiency in patients with early PD was similar or higher than the prevalence reported in previous studies.

"We confirm a high prevalence of vitamin D insufficiency in patients with recent onset of PD, during the early clinical stages in which patients do not require symptomatic therapy," the authors conclude. "Furthermore, vitamin D concentrations did not decrease but instead increased slightly over the course of follow-up. This provides evidence that during early PD, vitamin D concentrations do not decrease with disease progression."

Journal Reference:

1. Marian L. Evatt; Mahlon R. DeLong; Meena Kumari; Peggy Auinger; Michael P. McDermott; Vin Tangpricha; for the Parkinson Study Group DATATOP Investigators. High Prevalence of Hypovitaminosis D Status in Patients With Early Parkinson Disease. Arch Neurol, 2011; 68 (3): 314-319 DOI: 10.1001/archneurol.2011.30

New research into the neurodegenerative disease, multiple sclerosis (MS) offers new insight into the link between sunlight, vitamin D3, and MS risk and severity. The research, published in the European Journal of Immunology, studies the relationship between the sunlight-dependent vitamin D3 hormone, immune cells, and the risk and severity of autoimmunity in an experimental model.

Expensive first-line treatments for MS modestly reduce the frequency of autoimmune attacks but do not slow disease progression, when the patient's immune system operates against the body's own tissues. More expensive second-line treatments slow disease progression but carry high risks.

The origin of MS attacks remains unknown. However, new research indicates that a patient's vitamin D3 supply (derived mainly from sunlight exposure) is strongly related to disease activity; the fewest attacks and slowest progression occurred in patients with the highest vitamin D3 supplies. This research suggests that increasing vitamin D3 supplies might be a safe, effective and inexpensive therapy for MS.

"MS is a genetically and immunologically complex disease," said lead author Dr. Colleen Hayes from the University of Wisconsin-Madison. "It is currently incurable, but environmental factors, such as vitamin D3, may hold the key to preventing MS and reducing the impact of the disease in MS patients."

Dr Hayes' team originally suggested that the sunlight dependent hormone D3 (1,25-dihydroxyvitamin D3) may restrain the autoimmune attacks that cause MS based on the strong negative correlation between sunlight exposure and MS prevalence, the need for UV light to catalyze vitamin D3 formation, and the presence of receptors for the vitamin D3 hormone in T lymphocytes. They proposed that the vitamin D3 hormone might act on these receptors to control the T lymphocytes responsible for autoimmunity.

"Our new study investigated the protective effects of the vitamin D3 hormone in an experimental model of MS when the hormone receptor was either present or absent in T lymphocytes. We found that the hormone's protective effects were only evident when these receptors were present in autoimmune T lymphocytes. Our new data suggest that an action of the vitamin D3 hormone directly on pathogenic T cells leads to elimination of these cells," said Hayes. Actions of the vitamin D3 hormone on other immune cells have not been ruled out, but such actions were not sufficient for protection from autoimmunity if the hormone could not act on the pathogenic T cells.

This information is important because it provides a plausible biological explanation for the negative correlation between UV light exposure and MS disease risk and severity," concluded Hayes. "My research group and others around the world are building the scientific knowledge base needed to devise vitamin D-based strategies to prevent and treat MS" she adds. "There are many uncertainties and unanswered questions. However, understanding how sunlight and vitamin D3 may be working at the molecular level contributes greatly to our knowledge base and brings us closer to the goal of preventing this debilitating disease."

Journal Reference:

1. Christopher G. Mayne, Justin A. Spanier, Lance M. Relland, Calvin B. Williams, Colleen E. Hayes. 1,25-Dihydroxyvitamin D3 acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis. European Journal of Immunology, 2011; 41 (3): 822 DOI: 10.1002/eji.201040632

NewsPsychology (Feb. 8, 2011) — Much of the devastation of stroke and head trauma is due to damage caused the overproduction of a substance in the brain called glutamate. Preventing this damage has been impossible, until now, as many drugs don’t cross the so-called blood-brain barrier, and those that do often don’t work as intended. But a method originally devised at the Weizmann Institute of Science may, in the future, offer a way to avert such glutamate-induced harm.

Prof. Vivian I. Teichberg of the Institute’s Neurobiology Department first demonstrated a possible way around these problems in 2003. Glutamate — a short-lived neurotransmitter — is normally all but absent in brain fluids. After a stroke or injury, however, the glutamate levels in brain fluid become a flood that over-excites the cells in its path and kills them. Instead of attempting to get drugs into the brain, Teichberg had the idea that one might be able to transport glutamate from the brain to the blood using the tiny “pumps,” or transporters, on the capillaries that work on differences in glutamate concentration between the two sides. Decreasing glutamate levels in blood would create a stronger impetus to pump the substance out of the brain. He thought that a naturally-occurring enzyme called glutamate-oxaloacetate transaminase (GOT, for short) could “scavenge” blood glutamate, significantly lowering its levels. By 2007, Teichberg and his colleagues had provided clear evidence of the very strong brain neuroprotection that oxolacetate (a chemical similar to GOT) afforded rats exposed to a head trauma.

Two new studies — conducted by Francisco Campos and others from the lab of Prof. Jose Castillo in the University of Santiago de Compostela, Spain — now provide a definitive demonstration of Teichberg’s results. In the first, the scientists conclusively showed that oxoloacetate injected into rats with stroke-like brain injuries reduces glutamate levels both in the blood and in the affected brain region, while significantly lessening both cell death and the swelling that can accompany stroke. In the second, a team of neurologists in two different hospitals checked the levels of glutamate and GOT in several hundred stroke victims who were admitted to their hospitals. They found that the most significant predictor of the prognosis — how well they would recover at three months and how much brain damage they would suffer — was the levels of these two substances. High glutamate levels correlated with a poor outcome, high GOT levels with a better one.

The overall implication of these two papers is that administering GOT might improve a patient’s chances of recovering, as well as speeding up the process. In addition to stroke and head trauma, a number of diseases are characterized by an accumulation of glutamate in the brain, including Alzheimer’s disease, Parkinson, multiple sclerosis, epilepsy, glaucoma, certain brain tumors and amyotrophic lateral sclerosis, and there is hope that, in the future, treatments to scavenge glutamate could relieve the symptoms and improve the outcomes for a number of neurological problems. Yeda, the technology transfer arm of the Weizmann Institute, holds a patent for this method.

Prof. Vivian I. Teichberg’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Carl and Micaela Einhorn-Dominic Brain Research Institute; and the Legacy Heritage Fund Program of the Israel Science Foundation. Prof. Teichberg is the incumbent of the Louis and Florence Katz-Cohen Professorial Chair of Neuropharmacology.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by Weizmann Institute of Science.

Journal References:

1. Francisco Campos, Tomás Sobrino, Pedro Ramos-Cabrer, Bárbara Argibay, Jesús Agulla, María Pérez-Mato, Raquel Rodríguez-González, David Brea, José Castillo. Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study. Journal of Cerebral Blood Flow & Metabolism, 2011; DOI: 10.1038/jcbfm.2011.3
2. Francisco Campos, Tomás Sobrino, Pedro Ramos-Cabrer, Mar Castellanos, Miguel Blanco, Manuel Rodríguez-Yáñez, Joaquín Serena, Rogelio Leira, José Castillo. High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke. Journal of Cerebral Blood Flow & Metabolism, 2011; DOI: 10.1038/jcbfm.2011.4

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.

People who spend more time in the sun and those with higher vitamin D levels may be less likely to develop multiple sclerosis (MS), according to a study published in the February 8, 2011, print issue of Neurology®, the medical journal of the American Academy of Neurology. MS is a chronic disease of the brain and spinal cord, usually with recurrent flare-ups of symptoms. It is often preceded by a first episode (or event) of similar symptoms lasting days to weeks.

"Previous studies have found similar results, but this is the first study to look at people who have just had the first symptoms of MS and haven't even been diagnosed with the disease yet," said study author Robyn Lucas, PhD, of Australian National University in Canberra. "Other studies have looked at people who already have MS — then it's hard to know whether having the disease led them to change their habits in the sun or in their diet."

The multi-site study involved 216 people age 18 to 59 who had a first event with symptoms of the type seen in MS. Those people were matched with 395 people with no symptoms of possible MS who were of similar ages, of the same sex and from the same regions of Australia.

The participants reported how much sun they were exposed to during different periods of their lives, and researchers also measured the amount of skin damage participants had from sun exposure and the amount of melanin in their skin. Vitamin D levels (from sun exposure, diet and supplement use) were measured by blood tests.

The risk of having a first event, diagnosed by a doctor, ranged from approximately two to nine new cases for every 100,000 people per year in this study. The reported UV light exposure of participants ranged from about 500 to over 6,000 kilojoules per meter squared. The researchers found that the risk of having a diagnosed first event decreased by 30 percent for each UV increase of 1,000 kilojoules. They also found that people with most evidence of skin damage from sun exposure were 60 percent less likely to develop a first event than the people with the least damage. People with the highest levels of vitamin D also were less likely to have a diagnosed first event than people with the lowest levels.

Studies have shown that MS is more common in latitudes further away from the equator, and this has been confirmed in Australia.

"Added together, the differences in sun exposure, vitamin D levels and skin type accounted for a 32-percent increase in a diagnosed first event from the low to the high latitude regions of Australia," Lucas said.

Lucas noted that the effects of sun exposure and vitamin D acted independently of each other on the risk of first event. "Further research should evaluate both sun exposure and vitamin D for the prevention of MS," Lucas said.

Lucas also stated that people should continue to limit their sun exposure due to skin cancer risks. She also noted that the risks of tanning beds far outweigh any possible protective effect against MS. Exposure to the sun has not been shown to benefit people who already have MS.

The study was supported by the U.S. National Multiple Sclerosis Society, the National Health and Medical Research Council of Australia, the ANZ William Buckland Foundation and Multiple Sclerosis Research Australia.

Journal Reference:

1. R. M. Lucas, A.- L. Ponsonby, K. Dear, P. C. Valery, M. P. Pender, B. V. Taylor, T. J. Kilpatrick, T. Dwyer, A. Coulthard, C. Chapman, I. van der Mei, D. Williams, A. J. McMichael. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology, 2011; 76 (6): 540 DOI: 10.1212/WNL.0b013e31820af93d

If you think histamines are your nemesis during allergy season, here's something that might change your perspective. New research published in the Journal of Leukocyte Biology shows that histamine could be an important molecule to developing new treatments for multiple sclerosis (MS). In the study, the scientists analyzed the role of histamine in an animal model of multiple sclerosis and found that histamine plays a critical role in preventing MS or lessening its effects.

"We hope that our study will help design new therapies for autoimmune diseases and in particular MS, for which there is still not a definitive cure," said Rosetta Pedotti, MD, Ph.D., a researcher involved in the work from the Neuroimmunology and Neuromuscular Disorders Unit at the Neurological Institute Foundation Carlo Besta in Milan, Italy.

Histamine is a neurotransmitter involved in allergic reactions and other physiological and pathological processes. It is best known for the role it plays in hypersensitivity reactions like allergies, and it generally works by dilating blood vessels and making vessel walls permeable so immune cells can move more easily. Scientists studied the direct effects of histamine and two similar molecules that bind specifically on histamine receptors 1 or 2. Using a mouse model of MS, researchers generated MS-causing T lymphocytes and then treated these cells with histamine or the two other molecules. The effects of these treatments were evaluated by T cell functions analysis including proliferation, cytokine production, intracellular signaling pathways activation, and adhesion to brain vessels. Results showed that histamine reduces the proliferation of myelin autoreactive T lymphocytes and the production of interferon-gamma, a crucial cytokine involved in brain inflammation and demyelination. Additionally, histamine reduced the ability of myelin autoreactive T cells to adhere to inflamed brain vessels, a crucial step in the development of MS.

"This research is very exciting for several reasons. First, it points to unexpected connection between pathways involved in autoimmunity and allergy and suggests previously unrecognized connections between these very different types of immune responses. Second, while extending studies in animal models such as these to humans takes substantially more work, these new data point to a potentially novel drug target for MS and possibly other autoimmune or central nervous system diseases," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology.

Journal Reference:

1. M. Lapilla, B. Gallo, M. Martinello, C. Procaccini, M. Costanza, S. Musio, B. Rossi, S. Angiari, C. Farina, L. Steinman, G. Matarese, G. Constantin, R. Pedotti. Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation. Journal of Leukocyte Biology, 2010; 89 (2): 259 DOI: 10.1189/jlb.0910486

 New research from the University of North Carolina at Chapel Hill School of Medicine describes a key molecular mechanism in nerve fibers that ensures the rapid conductance of nervous system impulses.

The findings appear online Jan. 27, 2011 in the journal Neuron.

Our hard-wired nerve fibers or axons rely on an insulating membrane sheath, the myelin, made up of fatty white matter to accelerate the rate of transmission of electrical impulses from the brain to other parts of the body.

Myelin thus acts to prevent electrical current from leaking or prematurely leaving the axon. However, the myelin surrounding the axon isn't continuous; there are regularly spaced unmyelinated gaps about 1 micrometer wide along the axon. These unmyelinated regions named as nodes of Ranvier are where electrical impulses hop from one node to the next along the axon, at rates as fast as 160 meters per second (360 mph).

Determining exactly how the nodes of Ranvier function and how they are assembled, has fired the interest of neuroscientists for more than a century," said UNC neuroscientist Manzoor Bhat, PhD, Professor of Cell and Molecular Physiology in the UNC Neuroscience Research Center. "The answers may also provide important clues to the development of targeted treatments for multiple sclerosis and other disorders involving demyelination and/or disorganization of nodes of Ranvier."

Bhat and colleagues focused on a protein called Neurofascin 186, which accumulates in the membranes of axons at the nodes of Ranvier. Together with proteins Ankyrin-G and sodium channels, these molecules form a complex that facilitates passage of sodium ions through the channels in axons, thus making them paramount for the propagation of nerve impulses along myelinated nerve fibers.

Bhat's team had previously identified a homolog of Neurofascin in laboratory studies of Drosophila nerve fibers, and because its in vivo function had not been clearly defined in a mammalian system, they decided to study the function of this protein in laboratory mice.

Using targeted gene deletion methods, the UNC scientists genetically engineered mice lacking Neurofascin 186 in their neurons. "This caused the failure of sodium channels and Ankyrin-G to accumulate at the nodes of Ranvier. The result was paralysis, as there was no nerve impulse conductance," Bhat said.

According to Bhat, Neurofascin is an adhesion molecule that serves as the nodal organizer. "Its job is to cluster at the nodes of Ranvier. In doing so, it brings together sodium channels and Ankyrin-G where they interact to form the nodal complex. And if you don't have this protein, the node is compromised and there is no impulse propagation along the axon."

In further analysis, the researchers identified another important function of the nodes of Ranvier in myelinated nerve cells: to act as barriers to prevent the invasion of the nodal gap by neighboring paranodal molecular complexes. "So this tells us that sodium channels, Neurofascin 186, and Ankyrin-G must always remain in the node to have functional organization. If they don't, the flanking paranodes will move in and occupy the nodal gap and block nerve conduction," Bhat said.

The UNC neuroscientists see clinical implications for human disease. "In MS, for example, the proteins that make up the nodal complex start diffusing out from their normal location once you start losing the myelin sheath. If we can restore the nodal complex in nerve fibers, we may be able to restore some nerve conduction and function in affected axons." Their future studies are aimed at understanding whether the nodal complex could be reorganized and nerve conduction restored in genetically modified mutant mice.

"The discovery of an essential gap protein is exciting because it opens up the possibility that tweaking the protein could restore normal gap function in people with multiple sclerosis and other diseases in which the myelin sheaths and gaps deteriorate over time," said Laurie Tompkins, PhD, who oversees Manzoor Bhat's and other neurogenetics grants at the National Institutes of Health.

Support for the research came from the National Institute of General Medical Sciences, the National Institute of Neurological Disorders & Stroke of the National Institutes of Health and the National Multiple Sclerosis Society.

UNC co-authors are postdoctoral fellow Courtney Thaxton, PhD; research specialist, Anilkumar Pillai; and graduate student, Alaine Pribisco. Dr. Jeffrey Dupree, assistant professor at Virginia Commonwealth University, collaborated in these studies.

Journal Reference:

1. Courtney Thaxton, Anilkumar M. Pillai, Alaine L. Pribisko, Jeffrey L. Dupree, Manzoor A. Bhat. Nodes of Ranvier Act as Barriers to Restrict Invasion of Flanking Paranodal Domains in Myelinated Axons. Neuron, 2011; 69 (2): 244-257 DOI: 10.1016/j.neuron.2010.12.016

A new guideline from the American Academy of Neurology recommends using plasma exchange to treat people with severe relapses in multiple sclerosis (MS) and related diseases, as well as those with certain kinds of nerve disorders known as neuropathies.

The guideline is published in the January 18, 2011, print issue of Neurology®, the medical journal of the American Academy of Neurology.

Plasma exchange, formally known as plasmapheresis, is the process of taking blood out of the body, removing constituents in the blood's plasma thought to be harmful, and then transfusing the rest of the blood (mainly red blood cells) mixed with replacement plasma back into the body.

The guideline recommends doctors consider using plasma exchange as a secondary treatment for severe flares in relapsing forms of MS and related diseases. The treatment was not found to be effective for secondary progressive and chronic progressive forms of MS.

According to the guideline, doctors should offer plasma exchange for treatment of severe forms of Guillain-Barré syndrome and for temporary treatment of chronic inflammatory demyelinating polyneuropathy. Plasma exchange may also be considered for treatment of some other kinds of inflammatory neuropathies.

"These types of neurologic disorders occur when the body's immune system mistakenly causes damage to the nervous system. Plasma exchange helps because it removes factors in the plasma thought to play a role in these disorders," said guideline lead author Irene Cortese, MD, a neurologist with the National Institutes of Health in Bethesda, Md., and a member of the American Academy of Neurology.

The guideline authors also looked at the use of plasma exchange for other neurologic disorders, including myasthenia gravis and pediatric autoimmune neuropsychiatric disorders (PANDAS), but there was not enough evidence to determine whether it is an effective treatment.

Side effects of plasma exchange include infection and blood-clotting issues.

The guideline was endorsed by the American Association of Neuromuscular and Electrodiagnostic Medicine. The National Multiple Sclerosis Society endorsed the section of the guideline that relates to the use of plasma exchange for multiple sclerosis.

Journal Reference:

1. I. Cortese, V. Chaudhry, Y.T. So, F. Cantor, D.R. Cornblath, A. Rae-Grant. Evidence-based guideline update: Plasmapheresis in neurologic disorders: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 2011; 76: 294-300 DOI: 10.1212/WNL.0b013e318207b1f6

— Women who have multiple sclerosis (MS) are more likely to have a gene associated with multiple sclerosis than men with the disease and it is this gene region where environment interacts with the genetics, according to a study published in the January 5, 2011, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Research has shown that the number of people diagnosed with MS has been rising, and the rate has been rising faster for women than for men.

The cause of MS is not known, but evidence suggests that it is triggered by environmental factors in people who are genetically susceptible to the disease. The main gene associated with MS is the human leukocyte antigen (HLA) class II gene, but most of the risk comes from interaction of both parental genes.

The study examined the HLA genes of 1,055 families with more than one person with MS in the family. The genes of 7,093 people were tested, which included 2,127 people with MS. The researchers looked at what the HLA genes were for the people with and without MS, whether people with MS inherited the susceptibility gene from their mother or their father, and what the relationship was between people in the same family with MS.

The researchers found that women with MS were 1.4 times more likely to have the HLA gene variant associated with MS than men with MS. A total of 919 women and 302 men had the HLA gene variant, compared to 626 women and 280 men who did not have the gene variant. This fits with other research by this research group showing that the environment interacts with this gene region to produce modification in risk associated with it. This appears to be an epigenetic mechanism.

"Our findings also show women with the HLA gene variant are more likely to transmit the gene variant to other women in their families than to men," said study author George C. Ebers, MD, FMedSCi, of the University of Oxford in the United Kingdom and a member of the American Academy of Neurology.

The researchers also determined that second-degree relatives such as aunts and their nieces or nephews were more likely to inherit the gene variant than first-degree relatives such as siblings or parents and children.

"It appears that the less the genetic sharing between individuals, the higher the interaction is between female sex and inheritance of the HLA gene variant," said Orhun Kantarci, MD, of the Mayo Clinic in Rochester, Minn., and a member of the American Academy of Neurology, who wrote an editorial on the study. "These findings pave the way for future studies of these genes, hopefully to advance our understanding of inheritance of complex diseases such as MS."

The study was supported by the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Society of the United Kingdom.

Journal Reference:

1. M.J. Chao et al. MHC transmission Insights into gender bias in MS susceptibility. Neurology, January 5, 2011 DOI: 10.1212/WNL.0b013e318207b060

Eating purple fruits such as blueberries and drinking green tea can help ward off diseases including Alzheimer's, Multiple Sclerosis and Parkinson's, a University of Manchester report claims.

New research from Professor Douglas Kell, published in the journal Archives of Toxicology, has found that the majority of debilitating illnesses are in part caused by poorly-bound iron which causes the production of dangerous toxins that can react with the components of living systems.

These toxins, called hydroxyl radicals, cause degenerative diseases of many kinds in different parts of the body.

In order to protect the body from these dangerous varieties of poorly-bound iron, it is vital to take on nutrients, known as iron chelators, which can bind the iron tightly.

Brightly-coloured fruits and vegetables are excellent sources of chelators, as is green tea, with purple fruits considered to have the best chance of binding the iron effectively .

However, despite conflicting reports, the widely-publicised benefits of red wine seem to work in a different way, and have no similar benefits, Professor Kell's paper noted.

This new paper is the first time the link has been made between so many different diseases and the presence of the wrong form of iron, and gives a crucial clue as to how to prevent them or at least slow them down.

Professor Kell argues that the means by which poorly-liganded iron accelerates the onset of debilitating diseases shows up areas in which current, traditional thinking is flawed and can be dangerous.

For instance, Vitamin C is thought to be of great benefit to the body's ability to defend itself against toxins and diseases.

However Professor Kell, who is Professor of Bioanalytical Science at the University, indicates that excess vitamin C can in fact have the opposite effect to that intended if unliganded iron is present.

Only when iron is suitably and safely bound ("chelated") will vitamin C work effectively.

Professor Kell said: "Much of modern biology has been concerned with the role of different genes in human disease.

"The importance of iron may have been missed because there is no gene for iron as such. What I have highlighted in this work is therefore a crucial area for further investigation, as many simple predictions follow from my analysis.

"If true they might change greatly the means by which we seek to prevent and even cure such diseases."

Journal Reference:

1. Douglas B. Kell. Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples. Archives of Toxicology, 17 August 2010 DOI: 10.1007/s00204-010-0577-x