MS news and research
This page documents breaking multiple sclerosis news and research stories as they occur during the month.
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The U.S. Supreme Court deferred a decision on whether to hear an appeal by Teva Pharmaceutical Industries Ltd. that aims to delay generic competition to its top-selling Copaxone multiple-sclerosis drug.
The justices took no action on Teva’s bid for a hearing and are now scheduled to consider the case at their March 21 private conference, according to the court’s public docket.
Teva is seeking to revive a patent that would protect Copaxone from generic rivals until September 2015. Without that patent, Teva will lose legal protection this May on Copaxone, which brings in $3.2 billion in annual U.S. sales and accounts for more than half the company’s profit.
Teva is battling drugmakers that are planning to offer generic versions in May: Momenta Pharmaceuticals Inc, which has developed a version with Novartis AG’s Sandoz, and Mylan Inc.
The court issued a list of orders today from its March 7 conference. The Teva case was originally scheduled for consideration at that conference. The court, which often defers decisions on pending appeals, is scheduled to issue its next set of orders on March 24.
A ruling last year by the U.S. Court of Appeals for the Federal Circuit upheld four Teva patents that expire in May while invalidating a separate patent that would have blocked generic competition until September 2015.
In November, Chief Justice John Roberts refused to put the Federal Circuit ruling on hold while the high court decided whether to take up Teva’s appeal.
The case is Teva v. Sandoz, 13-854.
Source: Bloomberg ©2014 BLOOMBERG L.P (11/03/14)
Synthetic Biologics Inc. has announced that the U.S. Patent & Trademark Office has issued U.S. Patent No. 8658627 entitled Pregnancy Hormone Combination for Treatment of Autoimmune Diseases to the Regents of the University of California (UCLA). The patent includes claims to the use of the Company's drug candidate Trimesta™ (oral estriol) in conjunction with a gestagen for the treatment of multiple sclerosis (MS) and other autoimmune diseases. The patent also includes a claim for the administration of Trimesta™ a gestagen and a third standard of care MS agent such as glatiramer acetate injection (Copaxone®) interferon beta-1a (Avonex® Rebif®) interferon beta-1b (Betaseron® Extavia®) or sphingosine-1-phosphate receptor modulator (Gilenya®). Through its wholly owned subsidiary Synthetic Biologics holds the exclusive license to the newly issued U.S. Patent 8658627 as well as U.S. Patents 8372826 and 6936599 and pending patents for MS and other autoimmune diseases covering the uses of its oral estriol candidate Trimesta™.
In an on-going randomized double-blind placebo-controlled Phase II clinical trial for the treatment of women with relapsing-remitting MS patients enrolled at 15 centers in the U.S. are administered either Trimesta™ in combination with Copaxone® and progesterone (a gestagen) or receive a placebo plus Copaxone®. Lead Principal Investigator of the clinical trial Rhonda Voskuhl M.D. Professor Department of Neurology Jack H. Skirball Chair in Multiple Sclerosis Research and Director Multiple Sclerosis Program at the UCLA School of Medicine is scheduled to present topline results from this trial at the American Academy of Neurology's (AAN) 66th Annual Meeting in Philadelphia on April 29 & 30 2014 as part of the AAN Emerging Science program. The clinical trial is supported by grants exceeding $8 million awarded primarily by the National Multiple Sclerosis Society (NMSS) in partnership with the NMSS's Southern California chapter and the National Institutes of Health.
"Claims in this new patent further expand Synthetic Biologics' intellectual property related to our oral estriol candidate Trimesta™ for the treatment of MS and other autoimmune diseases" stated Jeffrey Riley Chief Executive Officer at Synthetic Biologics. "Our objective has been to continue to strengthen our intellectual property covering oral estriol and this patent is an achievement in that direction."
Source: Synthetic Biologics Inc (11/03/14)
New oral treatment can be offered as an alternative to currently available injectable treatment options.
The Scottish Medicines Consortium (SMC) today published its advice that Aubagio® (teriflunomide) 14 mg tablets has been accepted for use by NHS Scotland for the treatment of adults with relapsing remitting multiple sclerosis (RRMS), as an alternative to the currently available treatment options beta interferon or glatiramer acetate. The guidance does not include patients with highly active MS.
The guidance published by the SMC today represents an important step in improving the standard of care available to people with MS. "MS is a real concern in Scotland as it is a debilitating disease which has a high prevalence. This is good news for people with MS in Scotland and a significant milestone in improving the care of MS patients here," said Dr. Belinda Weller, Consultant Neurologist, Western General Hospital, Edinburgh.
Scotland has among the highest prevalence of MS in the world, with around 10,000 people living with MS in the country. Eighty-five percent of people with MS are initially diagnosed with RRMS and people with this type of MS experience approximately one or two relapses per year. Around half of all relapses may leave people with lingering problems and disability may accumulate over time.
Aubagio is the first medicine in Genzyme's pipeline of MS therapies to receive final SMC guidance and become available to patients in Scotland. "This is a very exciting time and the launch of Aubagio represents an important milestone for Genzyme as we provide new options to the MS community. Our commitment to improving the lives of people with MS goes beyond advancing treatment options, and we have a patient support programme underway to further support patients with adherence," said Brendan Martin, General Manager for Genzyme UK and Ireland.
Source: Genzyme (11/03/14)
An award-winning writer and scientist believes a deficiency of Vitamin D in pregnant women is behind the increase in conditions such as MS, diabetes, schizophrenia and asthma.
Scientists often liken the process of discovery to doing a jigsaw. At first, few pieces fit and the picture is a mystery. Then suddenly two or three pieces lock together and an image starts to take shape.
This is what is happening in the study of apparently unrelated, chronic diseases such as multiple sclerosis, schizophrenia, diabetes and asthma. These conditions are increasingly common both in the UK and elsewhere; their causes have puzzled doctors and scientists for decades.
Now pieces of the jigsaw are starting to fit together – and they focus on vitamin D which is produced naturally in the skin when exposed to sunlight.
A deficiency in this crucial vitamin, thanks to our increasingly indoor lifestyles, is already blamed for the reappearance of rickets, the painful and deforming bone disease in children, in the UK. But gradually, evidence is emerging that links low vitamin D levels to a rise in a whole host of “modern” diseases, some of which were virtually unheard of in the pre-industrial era.
As a scientist and writer, I first realised the significance of vitamin D for prevention of ill-health some 12 years ago, at a time when it was only recognised as important for bone growth. I have researched and written extensively on the topic, including a report on the health benefits of sunlight - this at a time when official advice was to avoid the sun at all costs, especially when the sun is at its highest.
The report, published in 2004, gained support from the late Sir Richard Doll, the eminent epidemiologist who co-discovered the link between smoking and lung cancer. He had completed a clinical trial which found that people who took vitamin D supplements may live longer - and had he lived had wanted to do another. It has taken eight years to get that clinical trial started with Professor Julian Peto of the London School of Hygiene and Tropical Medicine. Called VIDAL, the trial is looking at benefits of supplementation and for any increase in life expectancy in over 65s.
Highlighting the benefits of vitamin D has led to at least some degree of change in official attitudes. We are now advised to spend some time in the sun at midday, while vitamin D supplements are advised for breastfed (but not bottlefed) babies from the first month of life.
My belief is that we could go much further – that vitamin D, given freely to all women in pregnancy, could be used to curb or prevent some major diseases including multiple sclerosis, diabetes, schizophrenia, asthma and several cancers; and that it might also be used to treat established disease, at least in early stages.
One crucial piece in the jigsaw has come from the study of birthdays. Links between birthdays and future life events have long been the territory of clairvoyants and mediums; and when evidence first emerged about a decade ago that people born at the end of winter were more likely to get multiple sclerosis and those born in autumn less so, many scientists found it hardly credible.
“It looked as if we were interested in star signs and futurology,” said George Ebers, emeritus professor in the Department of Department of Clinical Neurology at the Wellcome Trust Centre for Human Genetics, University of Oxford, whose career has never deviated from scientific correctness. “But now we know that MS is associated with end of winter births, when shortage of sunshine is demonstrable and vitamin D levels are lowest. This suggests, in line with other observations, that vitamin D protects against the disease.”
THE POWER OF THE SUMMER SUN
Summer sun is at its maximum in June and July but vitamin D, generated in the skin by sunlight, takes two or three months to get into the general circulation. So we reach our maximum level of vitamin D in about September. Babies born in October or November have the best chance of a relatively high level of vitamin D during their final months in the womb. And this, the birthday evidence suggests, can protect them from MS, while the risk is higher for babies born at the end of winter.
This seasonal pattern in the risk of MS has now been found in eight different countries including Australia, winning over previously sceptical scientists. Less well known is the link between end of winter birthdays and an increased risk of several other diseases. Studies of thousands of birthdays in Europe, Canada and Australia over some 30 years have found that people born at this time are also at greater risk of type 1 diabetes, coeliac disease (gluten intolerance), schizophrenia and autism.
For a long time experts did not know what to make of this data, since these diseases had no obvious links. But now more conditions are being added to this list by the Oxford team. Writing in the peer-reviewed journal, BMC Medicine, in July 2012, Professor Ebers, working with Dr Sreeram Ramagopalan, has shown that the risk of rheumatoid arthritis, a digestive disease called ulcerative colitis and a distressing condition called systemic lupus erythematosus follows the same pattern of seasonal births. These are all autoimmune diseases, which occur when the body is attacked by its own immune system. Diabetes type 1 is also an autoimmune disease and in the case of coeliac disease the immune reaction is to wheat in the bowel. To date, at least 18 autoimmune diseases have been linked to low vitamin D levels – more than enough to demonstrate a pattern.
''These immune-mediated diseases are one of the most common disease groups in modern economies today, affecting some 10% of the world population. Vitamin D deficiency is the most obvious risk factor” says Dr Ramagopalan. To test this theory Dr Ramagopalan has examined blood taken from the umbilical cords of 50 healthy babies born in November and 50 born in May when, after winter, levels of vitamin D are low. The May babies had a far higher frequency of newly generated white blood cells called T cells which are normally programmed to react against infection by an outside agent and to tolerate the body’s own tissues.
However certain types of T cells react against the body tissues and they may cause autoimmune disease later on if they persist. These unwanted T cells are normally removed from the body in the first year of life by a clever arrangement - they are deleted in the thymus gland, a process that requires vitamin D. So a low vitamin D level leaves the baby at risk. Dr Ramagopalan has explained his findings in detail in the open access, peer-reviewed PLOS Genetics, 2009, in which he writes: “The prevalence of diseases, such as multiple sclerosis, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis correlate positively with latitude and reduced ultraviolet radiation exposure which is the primary determinant of vitamin D levels.”
The scientific jigsaw is now making more sense, but some pieces still do not seem to fit. Why should schizophrenia, a mental health condition, be linked to season of birth? In fact the birthday evidence on schizophrenia has provided a vital scientific clue to a disease which has puzzled doctors for over 100 years. Researchers now recognise that schizophrenia also has features of an autoimmune disease in which the body attacks its own tissues.
Schizophrenia and MS are both diseases of the nervous system. In MS myelin nerve sheaths deep in the nervous system are attacked by an immune reaction. If this can happen in MS, surely it is not so strange that schizophrenia may be explained similarly by an immune attack on crucial areas of the brain.
Dr John McGrath, international expert in schizophrenia based at the University of Queensland, Australia, says the evidence suggests that sun exposure in pregnancy and early life protects against schizophrenia and “raises the tantalising prospect that optimising vitamin D status during pregnancy may lead to the primary prevention of the disease”. “Being born in the country where there is more opportunity for sun exposure is associated with a lower risk of schizophrenia - while moving subsequently to an urban area where more time is spent indoors does not seem to increase the risk,” he points out.
Could lack of vitamin D in pregnancy also explain autism? The latest evidence suggests that a low vitamin D level in the mother’s body during pregnancy may induce her immune system to make antibodies which can damage the baby’s brain, as well as causing certain genes to malfunction. Last month, Rhonda Patrick and Bruce Ames from the Children’s Hospital Oakland Research Institute, in California, published research findings that these genes normally make the chemical serotonin.
Too little of this neurotransmitter is associated with abnormal social behaviour while too much in the digestive tract causes sensitivity to foods which may explain some autistic children’s difficult eating habits.
Patrick and Ames, both well-respected scientists in the field of autism, suggest: “Supplementation with vitamin D and tryptophan [which is made into serotonin in the brain] is a practical and affordable solution to help autism and possibly ameliorate some of the symptoms of the disorder.”
But the vitamin D jigsaw puzzle is not finished yet. Some 15 or more different cancers have been consistently associated with low vitamin D levels in a way that accords with established criteria, according to epidemiologist Dr William B Grant, from the non-profit organisation the Sunlight Nutrition and Health Research Center in California. In his paper published in 2009, the link is most clearly seen in breast and bowel cancer. Insufficient vitamin D leads to loss of control of several genes which regulate proliferation of cancer cells and inhibit the cell cycle.
In fact there are more than 900 genes that Vitamin D is now known to switch on and off - and in doing so alters our vulnerability to disease. The large number of genes involved explains how so many quite different diseases can be caused by insufficient sunshine. In this way sunshine exposure directly alters the action of genes which may actually be passed on in their altered state – a newly understood process known as epigenetics. So it is possible to see how some diseases may emerge for the first time in one generation and be passed on to the next.
There is understandable opposition to these theories from some in the medical establishment. In an editorial published last December,the journal The Lancet argued that failure of “gold standard” clinical trials of vitamin D to treat disease in adults disproves the possibility that insufficient vitamin D is a causal factor.
In my view, this ignores a wealth of experimental and observational evidence associating low vitamin D levels with higher risk of certain diseases. Also, vitamin D given in adulthood cannot necessarily be expected to cure a condition that has arisen through lack of vitamin D in early life. This is an error in scientific reasoning which I call the The Lancet’s “gold standard fallacy”.
INDOOR LIFESTYLES BLAMED
At the same time researchers are finding links between vitamin D and chronic disease, the world is facing an epidemic of these same conditions, caused by our indoor lifestyles. Even in the height of summer people in cities often have sub-optimal levels of vitamin D, and so babies born at any time of year may develop these diseases. It’s well recognised that multiple sclerosis has become increasingly common in the UK over the last century. Today, in cloudy Orkney, off the north of Scotland, one in 150 women suffer from MS, believed to be the highest prevalence in the world.
Less well known is that a generation ago the disease was much less common in southern than in northern Europe. But MS has increased rapidly in the Mediterranean over recent years, reflecting the increased movement of people away from rural subsistence farming to town and a life in urban apartments. In the Greek island of Crete MS has increased almost four fold over the last generation.
One striking example of the rise in MS is in Iran where, after the Islamic revolution in 1979, women were compelled by law to wear the veil outdoors together with clothing covering most of the body. Between 1989 and 2006, the incidence of MS in Iran increased more than eight fold, from an incidence of about one case in 100,000 to nearly one in 10,000 in the city of Isfahan.
“The Islamic revolution can potentially explain the observed increase in MS incidence in Iran in just over 30 years,” said Dr Ramagopalan. “Veiled women have lower vitamin D levels compared to unveiled women, giving an increased risk of low vitamin D in pregnancy which can account for the increase in MS.”
There have been similar increases in other autoimmune diseases, some rare or even unknown a century ago. Type 1 diabetes has seen an annual 4 per cent increase across Europe in a generation, with larger increases in the under-fives and the number of cases in this age group expected to double between 2005 and 2020. Crohn’s disease, a life threatening inflammation of the bowel, has since the 1930s become increasingly common in most developed countries.
Between 1965 and 1997 the incidence of schizophrenia doubled in London’s Camberwell. Much, but not all, of the increase is attributed to second generation dark-skinned immigrants who have a five times greater risk of the disease than their parents or people with white skin. Dark skin blocks absorption of weak northern sunlight, preventing vitamin D synthesis.
Autism was also rarity a generation ago. Between 1988 and 1995 the incidence in UK children increased some five fold, according to a nationwide survey by a 1000 GPs; arguably such a large rise cannot all be explained as improvements or changes in diagnosis of the condition, which is generally held to be difficult to miss. A similar increase occurred in the United States in the 1990s.
Over the last generation there has also been a global increase in asthma. Tests on frozen blood show that the epidemic is not caused by changes in diagnosis. Allergic reactions to mixed pollens, animal dander and house dust mites have increased by 4.5 per cent per decade in the UK during last quarter of the 20th epidemic has been followed closely by a rapid increase in food allergy. In extreme cases allergy can cause anaphylactic shock which has increased in England by 50 per cent between 2001 and 2005.
Professionals dealing with overflowing clinics are talking about a 'double tsunami’ – a giant wave of asthma followed by a second wave of food allergy, suggesting that they are two parts of a continuing epidemic. Two distinguished professors, Augusto Litonjua and Scot Weiss, from Harvard University School of Medicine calculate that some 300 million people worldwide now suffer from asthma and blame social changes: “...as populations grow more prosperous and more westernised”, they say, “more time is spent indoors and there is less exposure to sunlight, leading to vitamin D deficiency, subsequently resulting in more asthma and allergy.”
Why has the wave of food allergy followed the wave of asthma rather than occurring simultaneously: and why are second generation immigrants more at risk of diseases such as schizophrenia or Crohn’s than their first generation parents? The new science of epigenetics explains how the environment can influence genes which are then passed on in an altered state, in apparent contradiction of classical genetics.
Women who are severely vitamin D deficient may pass on de-activated genes, which make their children more vulnerable to disease. Multiple sclerosis, Type 1 diabetes, Crohn’s, schizophrenia, autism, asthma and food allergy have all been increasing in the same overlapping time frame and all have links to low vitamin D and low sunshine exposure. A further 11 autoimmune diseases have been linked to serious vitamin D deficiency in an Oxford study published in BMC Medicine in 2013. This makes at least 18 autoimmune diseases clearly linked to low vitamin D levels - more than enough to demonstrate a pattern.
PREVENTION IS CRUCIAL
Although The Lancet may insist otherwise, some clinical trials have shown that people with MS, asthma or Crohn’s may do better or have fewer relapses when they take vitamin D, if disease is not too advanced. For example, MS begins with optic neuritis, a temporary form of blindness, in 20 per cent of cases. Doctors at Isfahan University, Iran, have shown in a clinical trial that giving vitamin D (about 7,000 IUs per day) at this early stage can reduce risk of a relapse in blindness by 68 per cent and lower the incidence of lesions and “black holes” in the brain. They are hopeful that vitamin D may delay the usual conversion of optic neuritis to subsequent MS. Symptoms of Crohns’ disease can be reduced dramatically by 5,000 IUs per day of vitamin D according to a clinical trial at the Center for Molecular Immunology, University of Pennsylvania. Another study at Massachusetts General Hospital, described in the journal Inflammatory Bowel Disease, 2013, shows that risk of surgery is reduced in Crohns’ patients who took a vitamin D supplement that increased their blood level to normal.
While the Lancet remains trapped in its “gold standard” fallacy, doctors working with these autoimmune diseases, previously sceptical, are now privately hopeful that vitamin D will prove to be a useful addition to treatment. But increasing vitamin D later in life cannot always restore what has been lost when vitamin levels are low: for example, in the case of diabetes type 1, an enterovirus may attack the islet cells in the pancreas that make insulin, wiping them out. This is why prevention is so crucial: the link between high vitamin D levels in pregnancy and a reduction in diabetes risk was shown as long ago as 2001.
BRITAIN'S CLOUDY SKIES ARE BAD NEWS
THE UK has least sunshine of almost any advanced economy; our cloudy weather is arguably one of the unhealthiest climates in the world. And even when the sun shines we spend too much time indoors, detained by our computers and TVs. Fear of sunlight has been spread by misguided advice from cancer charities urging people to “seek the shade” rather than enjoy the sun safely and often. Extensive use of suncreams since the 1970s, has reduced exposure to UVB, the part of sunlight which generates vitamin D. The Chief Medical Officer, Dame Sally Davies, has said she is “profoundly ashamed” at the return of rickets in the UK. But the increase in rickets is small compared with the pandemic of immune system disease, the cost of which can be calculated in billions. MS costs the UK £3 billion a year, type 1 diabetes £9 billion, and schizophrenia £12 billion IN 1942, when Britain was besieged by German submarines, the government was eager to maintain the nation’s health by providing all children with cod liver oil, the best natural source of vitamin D. Since then successive governments have pursued a false economy and restricted free supplies of vitamin D supplements to a small percentage of pregnant and breastfeeding women and under-fives who are on state benefits.
I believe a great advance could be made by returning to heroic wartime thinking, providing all pregnant women and babies with free vitamin D supplements. I would argue that an intensive programme reaching 80-90 per cent of people, as modern vaccinations do, would greatly reduce and might even virtually eradicate MS, type 1 diabetes and several other autoimmune diseases.
Even lesser measures could at least halt or slow the pandemic. At little cost, the government could encourage voluntary fortification of foods such as milk and bread with vitamin D and give better advice on benefits of sunshine and how to enjoy the sun safely. Failure to act soon will be a cause for profound national shame.
Source: Daily Telegraph © Copyright of Telegraph Media Group Limited 2014 (10/03/13)
$1M fund established for MS research(06/03/14)
The Multiple Sclerosis Society of Canada and The Centre for Drug Research and Development (CDRD) have formed a partnership to accelerate the pace of Canadian research in multiple sclerosis. The MS Society says it is establishing a $1 million fund with CDRD to help transform promising research discoveries in MS into therapies.
“Over many decades, we have funded MS research that has led to significant insights about how the disease works and novel therapies for people living with MS,” said Karen Lee, vice-president, research, MS Society of Canada. “Through our collaboration with CDRD, we will accelerate the translation of these insights to expedite the development of effective treatments that have the capacity to make a meaningful impact on the lives of people living with MS today.”
To address this, the MS Society is working with CDRD to identify the most promising scientific discoveries to date, and develop them into treatments and a cure for MS. CDRD, Canada’s first and only centre of its kind, has access to technologies and projects from researchers and institutions across the globe, which ensures they are in an optimal position to develop life-changing treatments.
In addition, CDRD attracts and motivates industrial partners to invest in and help accelerate drug development. CDRD operates a high-level, fully integrated facility that collaborates with over 40 international organizations and a network of more than 10,000 investigators who are all involved in translational research initiatives.
CDRD President and CEO, Karimah Es Sabar commented, “The critical value of all stakeholders coming together – from the investigators conducting the breakthrough research, to foundations, translational centres, industry, government, and of course patients themselves – cannot be overstated. The Multiple Sclerosis Society of Canada is an outstanding organization representing the patients, and CDRD is excited about our partnership and the impact it will have.”
“Focus on translational research is critical to ensuring that basic knowledge generated in the lab can find its way into the clinic,” said V. Wee Yong, MS researcher and professor at the Hotchkiss Brain Institute and Departments of Clinical Neurosciences and Oncology, University of Calgary. “It helps researchers like me build the right partnerships to move the right discoveries through the treatment development process.”
Source: Lab Product News © 2014 Business Information Group (06/03/14)
For a healthy nervous system, axons—the long projections of our nerve cells that run throughout our bodies—must be properly insulated.
Much like conventional power cords need electrical insulators around the conducting wires for efficient and effective transfer of current, axons rely on multiple bilayers of myelin to maintain a rapid and optimal transfer of impulses between, for instance, brain and organ, or spinal cord and muscle. These bilayers are composed of lipids (fat molecules), protein, and water.
“Basically, myelin is this multiple stacking of lipid bilayers,” says Dong-Woog Lee, a researcher in the chemical engineering department at the University of California, Santa Barbara. “They need to be compact, and with very little water between the bilayers.”
Lee and colleagues found that even the slightest change in the composition of these myelin bilayers affect their ability to insulate axons. Their findings could offer insights into demyelinating diseases, such as multiple sclerosis.
Stick Like Glue
To observe and measure the characteristics and differences between healthy and diseased myelin bilayers, they studied the ability of these layers to adhere to each other.
The researchers used a highly sensitive instrument, called the surface forces apparatus, that can measure interactions between membranes. The deposited a lipid bilayer on a mica substrate on each of the two opposing surfaces of the apparatus.
Then they immersed the setup in a buffer solution containing myelin basic protein (MBP), a biomolecule commonly found in myelin that gives them adhesive properties and plays a role in maintaining the optimal structure of the myelin sheath.
They brought the two bilayers close together, allowing them to stick to each other, and then pulled them apart, measuring the strength of the adhesion brought about by the MBP “glue” between the bilayers, and also the MBP’s adsorption—the ability of the MBP molecules to stick to the bilayers’ surfaces.
They performed this experiment with both healthy myelin and with “disease-like” myelin bilayers.
“A lipid bilayer simulating a normal or healthy myelin membrane adsorbs this protein much better than a lipid bilayer simulating a multiple sclerosis-type of myelin membrane,” says UC Santa Barbara researcher Kai Kristiansen, “meaning that the protein attaches more strongly to the lipid bilayer and can make two apposing lipid bilayers adhere more firmly to each other and at a smaller distance—which is highly desirable for a well functioning myelin around a neuron.”
Swelling and Multiple Sclerosis
One common characteristic of diseased myelin is swelling, due to various causes such as the autoimmune responses associated with multiple sclerosis and its variants, or in cases of infection or exposure to certain chemicals. Genetics also play a role in the health of myelin.
“When the disease progresses, people can see that they swell and eventually vesiculate, creating scars,” says Lee, who is lead author of the study published in the Proceedings of the National Academy of the Sciences.
The MBP layer between the lipid bilayers also swells with water that seeps in between the double lipid layers. Instead of being a compact, molecule-thick film, the MBP layer becomes more gel-like.
“And since there’s more water between the bilayers, their insulation property decreases,” says Lee. From there, impulses slow down along the axon, or dissipate before they reach their destinations, causing paralysis and loss of function.
Disease–related changes in the lipid domain structures’ size and distribution also causes irregular adsorption of MBP onto the lipid bilayers and weakens their adhesion properties. This in turn also leads to lower nerve insulation.
The next step, according to Jacob Israelachvili, professor of chemical engineering and of materials, is to develop a user-friendly bench-top instrument that could be used in hospitals and clinics to visualize the membranes of certain cells, both healthy and pathological, whose domain structure can be an indicator of the progression of a disease.
“We are currently planning a collaboration with a local hospital to provide us with such membranes, for example, from leukemic blood cells, that we would tag with a suitable fluorescent dye to enable this imaging,” he says.
Source: Futurity © 2014 Futurity (06/03/14)
When a pack of whip-thin girls zipped across the finish of a recent 1600-metre race, the smallest runner's legs wobbled like rubber, and she flopped into her waiting coach's arms. She collapses every time she races.
Kayla Montgomery, 18, was found to have multiple sclerosis three years ago. Defying most logic, she has gone on to become one of the fastest young distance runners in the United States - one who cannot stay on her feet after crossing the finish line.
Because MS blocks nerve signals from Montgomery's legs to her brain, particularly as her body temperature increases, she can move at steady speeds that cause other runners pain she cannot sense, creating the peculiar circumstance in which the symptoms of a disease might confer an athletic advantage.
But intense exercise can also trigger weakness and instability; as Montgomery goes numb in races, she can continue moving forward as if on autopilot, but any disruption, like stopping, makes her lose control.
“When I finish, it feels like there's nothing underneath me,” Montgomery said. “I start out feeling normal and then my legs gradually go numb. I've trained myself to think about other things while I race, to get through. But when I break the motion, I can't control them and I fall.”
At the finish of every race, she staggers and crumples. Before momentum sends her flying to the ground, her coach braces to catch her, carrying her aside as her competitors finish and her parents swoop in to ice her legs.
Minutes later, sensation returns and she rises, ready for another chance at forestalling a disease that one day may force her to trade the track for a wheelchair. MS has no cure.
Last month, Montgomery, a high school senior, won the North Carolina state title in the 3200 metres. Her time of 10 minutes 43 seconds ranks her 21st in the country. Her next major competition is the 5000 metres at the national indoor track championships in New York on March 14, when she hopes to break 17 minutes.
Her trajectory as a distance runner has been unusually ascendant.
“When she was diagnosed, she said to me, 'Coach, I don't know how much time I have left, so I want to run fast - don't hold back,'” said Patrick Cromwell, Montgomery's coach. “That's when I said, 'Wow, who are you?'”
At the time, Montgomery was one of the slowest on her team, completing her first 5-kilometre race in 24:29; by last November, she had run a 17:22, placing 11th in the regional qualifier for a national cross-country championships.
The diagnosis of MS came after Montgomery could not feel her legs after she fell playing soccer and shocks ran up her spine. She was on her school cross-country team and told her coach that her legs went numb when she ran.
“I said, 'Well, sweetie, that's kind of how running is, you feel the pain and then you don't, you just have to push through,'” Cromwell said. “But she said 'No, they stay numb.' I knew that wasn't normal, and that's when the doctor visits started.”
A magnetic resonance imaging exam revealed six lesions on Montgomery's brain and spine. With treatment, she went into remission and resumed racing.
Because Montgomery has played down her condition, few people understand her unusual racing finishes.
In the national indoor 5000-metre championship last year, officials forgot to catch her and she fell on her face, lying prostrate on the track until someone carried her away. Announcers speculated that she had a seizure. Some assume she is fainting. Others, she said, have simply called her a wimp.
She dismisses the attention.
“I didn't want to be treated differently, and I didn't want to be looked at differently,” she said.
In many ways, Montgomery's life resembles that of an ordinary high school track athlete. Before every race, she puts on the same lucky green sports bra and size 5 1/2 running shoes that carry her 155-centimetre frame.
She is deeply involved with her Methodist church, along with her younger sister and her parents, a nursing student and a pesticide salesman. Her school marks are strong and she logs 80 kilometres a week.
Though examples of elite athletes with MS are scarce, some have speculated that Montgomery's racing-induced numbness lends a competitive edge, especially given the improvement in her times since the diagnosis.
“The disease has no potential to make her physically more competitive,” said her neurologist, Lucie Lauve, who also said she did not know precisely why Montgomery collapsed after races. “If MS has made her a better athlete, I believe it is a mental edge.”
Cromwell, Montgomery's coach, said he thought that insensitivity to the pain of distance racing could be marginally advantageous.
“I think there's a benefit to numbness,” he said. “I don't know anyone in their right mind, though, who would trade this; who would say, 'Give me MS so I have a little bit of numbness after Mile 2.' But I think that's when she gets her strength.”
The numbness is particularly dire for midrace falls. At her state cross-country meet last year, she clipped the heel of a fellow runner in the lead pack and crashed. Facedown with her legs splayed, she could not get up.
Runners sprinted by, and she slipped from all-state contention. Seeing a rival pass was enough to get her to use a nearby fence to pull herself up and cruise into 10th place. It was a lesson in resilience. “Now I know I can do it,” she said. “It may take a little while, but if I fall, I know I can get up.”
Exercise is commonly recommended for MS patients, and Montgomery's doctor has cleared her for racing. However, some experts worry pushing to the point of collapse could have long-term drawbacks.
“When you push to your limit, your body usually sends pain signals to warn you that you're damaging tissues,” said Dr Peter Calabresi, director of the Multiple Sclerosis Centre at Johns Hopkins. He has not treated Montgomery.
“Pushing that limit is what endurance sports are all about. But if you can't feel those signals and push from tingling to extreme or prolonged numbness, you could be doing damage that we won't even know about until down the road. It's a paradox.”
Source: Brisbane Times Copyright © 2014 Fairfax Media (05/03/14)
Background: The relationship between cognitive impairment and disease course and severity of multiple sclerosis (MS) is not well understood.
Objective: The aim of the study was to evaluate whether cognitive complaints in different clinical phenotypes and severity stages of MS are associated with differences in the profile of cognitive impairment.
Methods: 196 MS patients (relapsing-remitting RRMS n=138; secondary progressive SPMS n=32; primary progressive PPMS n=26) with perceived cognitive deficits underwent neuropsychological assessment with the brief repeatable battery of neuropsychological tests (BRBNT). Mood, impact of the disease, and quality of life were evaluated with self-reports.
Results: Only minor differences were observed in the cognitive impairment profile of different disease phenotypes and different disease severity stages. RRMS patients performed better only in one cognitive test of the BRBNT, than patients with progressive disease types. When RRMS, SPMS, and PPMS groups were evaluated separately, PPMS showed more pronounced cognitive impairments than RRMS and SPMS. The relationships between cognitive impairment and severity of disability as well as duration of disease were weak.
Conclusion: MS patients with cognitive complaints tend to have a relatively similar cognitive impairment profile which is not dependent on the disease course and severity.
Eija Rosti-Otajärviemail address, Juhani Ruutiainen, Heini Huhtala, Päivi Hämäläinen
Source: Multiple Sclerosis Copyright © 2014 Elsevier Inc (03/03/14)
Although their oft-cited prior study found no causal relationship between venous abnormalities in the neck and multiple sclerosis (MS), University at Buffalo neurological researchers are strongly advocating more investigation.
Robert Zivadinov, MD, PhD, professor of neurology, and his colleagues cite mounting evidence that the extracranial venous system may play a role in a broad range of central nervous system disorders and aging.
“The full story and consequence of these venous abnormalities that disrupt normal blood flow will require much more research,” says Zivadinov, who also directs UB’s Buffalo Neuroimaging Analysis Center.
New Research Could Explore Risk Factors
Countering calls to abandon related research, Zivadinov has coauthored a debate article, “Potential Involvement of the Extracranial Venous System in Central Nervous System Disorders and Aging,” with Chih-Ping Chung, MD, PhD, of National Yang-Ming University in Taiwan, in BMC Medicine.
Zivadinov also published a related editorial, “Is There a Link Between the Extracranial Venous System and Central Nervous System Pathology?” in the same journal. He and Chung call for research examining the incidence and prevalence of venous abnormalities in relation to developmental and demographic factors, as well as cardiovascular, inflammatory and lifestyle risk factors.
Prior ‘Neurology’ Study Among Most Cited
In their July 2011 study, “Prevalence, Sensitivity and Specificity of Chronic Cerebrospinal Venous Insufficiency in MS,” published in Neurology, Zivadinov’s team found an increased prevalence of extracranial venous abnormalities in MS patients, but no evidence of causation.
Their paper is one of the top 10 articles in neurology and the second-most-cited paper in neurology in the past three years, according to Neuropenews, the news blog of the European Federation of Neurological Societies and the European Neurological Society.
“We have since developed a substantial body of work looking at these abnormalities in relation to Alzheimer’s disease, aging and other neurological diseases,” says Zivadinov.
“We believe our current studies on how these abnormalities impact central nervous system pathology will also prove to be of ongoing interest to the scientific community.”
Abnormalities May Impede Blood Flow From Brain
Extracranial venous abnormalities indicate chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by the narrowing of vessels that drain blood from the cranium.
Paolo Zamboni of the University of Ferrara in Italy was the first to hypothesize that the condition results in changes in blood flow patterns that eventually injure brain tissue and degenerate neurons, leading or contributing to MS.
Compared to Zamboni’s research, the UB study found much lower sensitivity and specificity rates of CCSVI in MS patients.
However, the UB team did find a much higher prevalence of CCSVI in progressive versus non-progressive MS patients, suggesting the condition may be a consequence, rather than a cause, of MS.
The research team included Department of Neurology co-authors Ralph H. Benedict, PhD, professor; Michael G. Dwyer III, PhD, assistant professor; David W. Hojnacki, MD, assistant professor; Bianca Weinstock-Guttman, MD, professor; as well as Murali Ramanathan, PhD, professor of pharmaceutical sciences.
Source: University Of Buffalo © 2014 University at Buffalo (28/02/14)>
Taking the contraceptive Pill may increase a woman’s chance of developing multiple sclerosis, researchers warn.
The risk of MS could be up to 50 per cent higher among women on the Pill, according to a new US study.
The findings also show young obese women are at greater risk of the disease, probably because they produce higher levels of a hormone known to regulate appetite.
Previous research had suggested that oral contraception could cut MS risk, or delay its onset.
MS is the most common disabling neurological condition, affecting almost 100,000 Britons – around 50 people are diagnosed each week.
It involves damage to myelin, a protective sheath surrounding nerve fibres of the central nervous system, meaning the body’s immune system attacks itself.
Symptoms range from mild, occasional illness involving numbness, muscle weakness and eye problems to rapid and severe deterioration, resulting in serious disability.
US researchers identified 305 women who had been diagnosed with MS during a three-year period.
Their use of the Pill – mainly a combination of two hormones – was compared with 3,050 women who did not have MS.
In total, 29 per cent of the women with MS and 24 per cent of those without MS had used hormonal contraceptives for at least three months in the three years before symptoms began.
Women who had used the Pill were 35 per cent more likely to develop MS than those who did not use them. Those who had used the contraceptives but had stopped at least one month before symptoms started were 50 per cent more likely to develop MS.
Lead researcher Dr Kerstin Hellwig said: ‘These findings suggest that using hormonal contraceptives may be contributing at least in part to the rise in the rate of MS among women.’
Previously animal research led experts to believe female hormones might delay the onset of MS, and a British study suggested Pill users had a 40 per cent lower risk.
The new research was presented at the American Academy of Neurology’s annual meeting in Philadelphia.
In a separate study at the same meeting, researchers looked at a possible link between obesity and MS, by checking the Body Mass Index (BMI) of study volunteers.
BMI was calculated for 210 people with MS and 210 people of the same age and sex who did not have MS at ages 15 and 20 and at the time of the study.
The study found that people who are obese at age 20 are twice as likely to later develop MS as people who are not obese.
The study found that people with higher BMI levels also had higher levels of leptin, a hormone made by fat tissue that regulates weight, appetite and immune response.
Study author Dr Jorge Correale, of the Raúl Carrera Institute for Neurological Research in Buenos Aires, Argentina, said ‘Leptin promotes inflammatory responses in the body, which could potentially explain the link between obesity and MS.’
Source: The Daily Mail © Associated Newspapers Ltd 2014 (28/02/14)
A casual conversation in a hockey locker room prompted a business partnership that may eventually help people suffering from multiple sclerosis and other neuro-degenerative diseases.
Joseph S. Erlichman, a biology professor at St. Lawrence University, and Mark L. Brackett, president of the Kinney Drug Inc. Foundation, are working with others to develop a drug to treat diseases such as MS and Amyotrophic Lateral Sclerosis, also known as Lou Gehrig’s Disease.
After playing hockey one evening, the two men discussed research that Mr. Erlichman and a few of his colleagues were conducting on live brain slices from mice.
The study focuses on observing how the compound cerium oxide affects neuro-damage that’s taken place in the mice. The rodents are observed after they’re placed on a motor-skill apparatus like a treadmill or balance beam to see if they show improvement after taking the cerium oxide.
For the past several years, students from SLU have been involved in that part of the research.
Mr. Erlichman said the results have been promising so far.
“We’ve been accruing an enormous amount of data,” he said. “We’ve found this has the potential to mitigate or decrease tissue damage or disease progression in a wide variety of pathologies.”
Essentially, the compound is effective at neutralizing free radicals that are associated with many pathological diseases, Mr. Erlichman said.
For multiple sclerosis, the compound appears to be as effective as Gilenya, a drug now used to treat the disease in humans, he said.
“We have also used the nanoparticles in the treatment of a mouse model of ALS with promising results,” he said.
In 2009 Mr. Brackett and Mr. Erlichman created the company Neuroredox, with Mr. Brackett serving as its chief executive officer.
Later they teamed up with Cerion Enterprises, a Rochester-based company, to create a new joint venture company, erion NRx, which will continue the necessary steps involved with developing the drug.
Other SLU professors have also been involved in the research, including William DeCouteau, Ana Y. Estevez, Karin Heckman and Matthew C. Skeels.
Upcoming steps include receiving approval from the Food and Drug Administration to test the drug’s effectiveness on humans. Determining whether the drug is toxic to humans will be a main factor in determining if it can be marketed to a pharmaceutical company and then sold to the public, Mr. Brackett said.
Finding a pharmaceutical company to invest in the product and applying for federal funding are other hurdles.
“You have to get all the ducks in a row,” Mr. Brackett said. “We have hired a consultant who has taken other drugs to market.”
Mr. Brackett, a former pharmacist, said he has been interested in neurological diseases for many years.
“These diseases cause a great deal of devastation and pain to families. We think we can help that,” he said.
Source: Watertown Daily Times (27/02/14)
Potential 'cure' for multiple sclerosis to be tested The National Center of Neurology and Psychiatry has developed a drug that it says might provide a cure to multiple sclerosis.
The center announced Monday that it will start a three-month clinical trial from March on nine patients. If the drug’s efficacy is confirmed, it will move on to a large-scale trial.
“We are hopeful as preliminary studies have produced very good results,” said Takashi Yamamura, head of the immunology department responsible for the drug’s development. About 2.5 million people around the world are estimated to suffer from the disease, which causes symptoms such as numbness, motion problems and vision loss. In Japan, there are an estimated 15,000 sufferers, including many young women, and the number is growing.
The autoimmune disease occurs when lymphocyte immune cells misidentify the body’s own cells as foreign. They attack nerve cells, causing inflammation and destroying them.
The drug developed by Yamamura stimulates a type of immune cell that softens the attacks by lymphocytes and creates a protein that suppresses inflammation. In the clinical trial, the drug will be drunk in powder form dissolved in water, according to the center.
Source: THE JAPAN TIMES © THE JAPAN TIMES LTD (26/02/14)
Patients who have used stem cell therapy to reverse the effects of multiple sclerosis are lobbying the Federal Government to provide the treatment in Australia.
A European trial has achieved a 95 per cent success rate, but Australian hospitals are reluctant to use it.
The treatment involves using haematopoietic stem cell therapy, where a patient’s stem cells are harvested from their blood, then an intense chemotherapy regime kills off the MS-ridden immune system, before the harvested stem cells are reinjected.
Neurologist Dr Colin Andrews was one of the first in Australia to use the treatmen, which is only suitable for patients with aggressive MS that existing medication cannot treat.
“We're rebooting the immune system and moving the cells we don’t want,” Dr Andrews said.
“Within a week to 10 days you've got a whole new immune system.”
Recent overseas studies have had a 95 percent success rate of stopping the disease.
The first eight patients in Australia had the treatment done at Canberra Hospital, but the hospital shut down the program half way through the ninth patient on the grounds it was unethical.
“What we’re doing here is harvesting the patient’s own cells, it’s not cells from elsewhere or any other source, so I can’t see there's an ethical issue,” Dr Andrews said. It leaves only one doctor in Australia offering the treatment, yet there are about 4000 sufferers, leaving many heading overseas for help.
But it is at huge cost.
“I had no choice, I was on a ticking time bomb, I didn’t know what to expect next, my health and my child is far more important so I had to go,” Melinda Beattie said.
She spent $65,000 to go to India for the treatment, while Andrew Price flew to the US spending $130,000.
Both their treatments were successful.
They've now formed an organisation to lobby the Federal Government, but MS Australia is refusing to support it at the current time.
“The procedure itself is still in a very experimental stage very much only works with a very small number of people,” Deb Cerasa from MS Australia said.
But Dr Andrews has defended the treatment.
“It’s a procedure, it’s not an experiment, something that’s been around for 10 years, it’s widely practiced throughout the rest of the world we don’t regard it as experimental,” he said.
Source: Yahoo! 7 News (26/02/14)
Some people are content to sit back and relax when they retire, maybe traveling or working in their gardens.
Others want to turn their talents toward helping others. That was true of Jana Gasiorkiewicz.
About seven months ago, Gasiorkiewicz became a certified yoga instructor. Several months ago, she launched her Yoga on a Chair classes.
But her practice targets patients with multiple sclerosis and similar medical conditions. The classes are conducted on chairs “because so many people can’t get down on the mat,” she explains.
“You don’t need the stamina (to stand),” she said. “Without overtaxing those already weakened limbs and your heart, you can bring some movement and build some heat without exhausting yourself.”
Gasiorkiewicz retired in 2011 after working for 20 years for the Kenosha Unified School District. The last 11 years were spent teaching French at Bradford High School. She has been teaching one French class at the University of Wisconsin-Parkside since September.
After retiring, she said she had more time and started going to yoga classes at YogaRoots Racine, 518 College Ave., in Downtown Racine.
Gasiorkiewicz’s daughter, Suzanne Selmo, had become a yoga therapist in California. Gasiorkiewicz, 65, received her instructor certification in July. But then the question became whom would she teach?
She said a friend’s husband has Parkinson’s disease, and he benefited from yoga.
“It gave me the idea to target my practice to a particular audience,” Gasiorkiewicz said. “When I looked into it, I found there were many more MS patients than Parkinson’s patients.”
Multiple sclerosis is an often-disabling central nervous system disorder. Symptoms range from abnormal fatigue to memory, attention and vision problems, according to the National Multiple Sclerosis Society. Some patients may suffer some form of paralysis, or need help from a cane or crutches to work, according to the organization.
Because people with MS may have a limited range of motion, or may not be able to lie on the floor on mats, Gasiorkiewicz teaches her classes on chairs.
A relative with MS died about six years ago. And Gasiorkiewicz said she learned a few years ago that a former coworker with MS had died.
“Those two women — their lives were so changed by MS. Those reasons were in the back of my mind,” she said.
Some patients have mild symptoms. Others, she said, are in wheelchairs. Two participants, a married couple from Kenosha, have said they both benefit from the classes. But only the wife has MS.
“For me, it’s strengthening, flexibility, balance, stress reduction,” she said. “If they would try it consistently, after a few months they would see the benefits would warrant setting aside a little money or time.”
Source: Journal Times © Copyright 2014, Journal Times (26/02/14)
Widespread pressure pain hypersensitivity in patients with MS with and without pain as sign of central sensitisation.(25/02/14)
OBJECTIVE: To determine the presence of widespread pressure hyperalgesia in multiple sclerosis (MS) patients with and without pain and its association with pain and fatigue.
METHODS: One hundred and eight (n=108) individuals with definite MS, 49 men and 59 women (mean age: 44±8 y) and 108 age- and sex matched healthy controls (mean age: 44±9 y) were included. Fifty patients (n=58, 54%) reported pain and 50 (46%) did not exhibit pain. Pressure pain threshold (PPT) was bilaterally assessed over supra-orbital, infra-orbital, mental, median, radial and ulnar nerve trunks, C5-C6 joint, second metacarpal and tibialis anterior muscle by an assessor blinded to the subject's condition. The intensity of pain was assessed with a numerical pain rate scale (0-10), fatigue was determined with the fatigue impact scale (FIS), and depression was evaluated with the Beck Depression Inventory (BDI-II).
RESULTS: The ANCOVAs revealed that PPT were significantly decreased bilaterally over the supra-orbital, infra-orbital, mental, median, ulnar, and radial nerve trunks, C5-C6 joint, second metacarpal and tibialis anterior muscles in patients with MS compared to healthy controls (all, P<0.001). No significant differences existed between MS patients with pain and those without pain (all P>0.944). Patients with pain exhibited higher fatigue and depression than those patients without pain (P<0.05). PPT was not associated with any clinical variable, i.e., pain, depression, or fatigue).
CONCLUSIONS: Our study found widespread pressure pain hyperalgesia in individuals with MS as compared to healthy controls. No differences existed between MS patients with pain and those without pain in the presence of widespread pressure sensitivity. Current results suggest that MS is associated with sensory hyper-excitability of the central nervous system or dysfunction in endogenous pain modulatory systems.
Fernández-de-Las-Peñas C1, Ortega-Santiago R, Ortíz-Gutiérrez R, Caminero AB, Salom-Moreno J, Arendt-Nielsen L.
Source: Clin J Pain. 2014 Feb 12 & Pubmed PMID: 24525905 (25/02/14)
Individuals who are suffering from Multiple Sclerosis might have a certain antibody inside their blood, perhaps permitting for early discovery with a blood test prior to any symptoms showing up. There is a potassium protein that contained the antibodies in question and they were found in over six of nearly 20 test subjects who did not have any MS symptoms during the time of testing. Yet each had ended up developing the disease by nine months after the test. Two other participants of the group ended up showing borderline existence of the antibodies.
The results of the entire group were measured against a control group of nearly 15 other people who were the same sex and age as the original group. These people did not have any of the unusual antibodies in their blood and none of them went on to develop MS. This test was held by a technical university located in Germany. The researchers plan on showing their findings at the American Academy of Neurology’s yearly meeting, which is set to be held in April.
Such findings are very positive for the sufferers of MS, as information might help lead to early exposure and also to possible positive treatment. Eventually there may even be prevention of Multiple Sclerosis. The research study’s leader, Dr. Viola Biberacher, stated that if such results could be repeated in bigger parts of the population, then the findings could possibly aid in finding MS earlier in patients. By discovering the disease before symptoms start to show up could mean that physicians and scientists might possibly be able to prepare and treat and maybe even stop some of the symptoms of MS.
These discoveries have also shown that antibodies that have developed in a protein known as KIR4.1, which has been discovered in several individuals with MS, came before the onset of the disease. This suggests a part of the auto antibody in the way of how MS might develop, Biberacher added.
Since the year 2008, Multiple Sclerosis diagnosis rates have risen almost 12 percent worldwide. There are over two and a half million people that are believed to be suffering from the incapacitating condition at this time. Presently there is not any sort of cure for MS either. It is an autoimmune disease which affects the insulating shields inside the cells of nerves throughout the spinal cord and brain.
It is believed that MS develops as the result of a genetic disposition, along with other exterior factors, such as having a deficiency of sun exposure. That seems to aid in the diseases advancement. Countries located in the northern part of the world, that have less sunlight seem to have a higher frequency of Multiple Sclerosis, with Canada having about 290 assessed cases for every 100,000 amount of their population. Sweden also has high rates of MS, with an estimated 190 cases for about every 100,000 individuals. But unlike these countries, doctors located in the United States are not obligated to report occurrences of the condition to the Centers for Disease Control. So the amount of official cases in America stays uncertain.
Biberacher is hopeful about treatments in the future. She stated that the next step of the process was to authorize findings in bigger groups and figure out just how many years there is before Multiple Sclerosis begins that the antibody response begins to start developing in the body. If the individuals who are suffering from Multiple Sclerosis do have such an antibody inside their blood, perhaps permitting for early discovery prior to any symptoms showing up will be available to them in the future.
Source: Guardian Liberty Voice (24/02/14)
Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results(21/02/14)
BACKGROUND: Clinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting.
OBJECTIVE: To evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS).
METHODS: The Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings.
RESULTS: In this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11-44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12 months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5 years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5 years.
CONCLUSIONS: Interim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice.
TRIAL REGISTRATION NUMBER: NCT00493298.
Butzkueven H1, Kappos L, Pellegrini F, Trojano M, Wiendl H, Patel RN, Zhang A, Hotermans C, Belachew S; on behalf of the TYSABRI Observational Program (TOP) Investigators.
Source: J Neurol Neurosurg Psychiatry. 2014 Feb 14. doi: 10.1136/jnnp-2013-306936. & Pubmed PMID: 24532785 (21/02/14)
Access to treatment and services varies remarkably for EU citizens diagnosed with multiple sclerosis, depending on which country they live in, according to a survey by the European Multiple Sclerosis Platform (EMSP).
The MS Barometer 2011, which has measured and compared wellbeing and quality of life for people living with multiple sclerosis in 33 European countries, including 26 EU member states, shows huge disparities in terms of access to treatment, therapies and employment.
While Germany overall came on top as the best country for people with multiple sclerosis in the EU, scoring 207 points, ahead of Sweden (184 points) and Austria (178), Bulgaria scored the fewest points (62 points), followed by Poland and Lithuania with 87 and 88 points, respectively.
Maggie Alexander, CEO of the EMSP, told EurActiv that the impact of having a condition such as multiple sclerosis is much more severe in countries that fail to provide the optimal treatment and services to help people maintain control of their disease, including remaining economically independent and fully participate in society.
“The EMSP will continue to drive forward effective collaborations with EU institutions and all those that share our commitment to escalate progress in the vital areas of research, healthcare and employment,” Alexander said.
“This will help to reduce the health inequalities that are faced by far too many of the nine million people in Europe living with neurodegenerative conditions,” EMSP’s CEO continued.
Multiple sclerosis is a potentially disabling disease. It strikes the white matter of the brain and spinal cord and affects the rest of the nervous system. According to the EMSP, multiple sclerosis has great consequences for society as more than one million people in Europe are affected indirectly through their role as carers and family members.
Younger people between 20 and 40 are the ones who are the most often diagnosed with multiple sclerosis. Women are diagnosed twice as often as men.
More than 120,000 people with multiple sclerosis live in Germany. This is more than in most other European countries. The EMSP said that Germany, with its long tradition of universal healthcare, provides strong protection for all disabled people.
When it comes to multiple sclerosis, the treatment in Germany is carried out by inter-disciplinary teams. The full cost of disease-modifying drugs is reimbursed by government without limits on duration of treatment and the treatment of symptoms is also fully covered. People also have unlimited access to rehabilitation.
Another positive fact about Germany is that good access to new medication and that specialised palliative care are offered while the country also scores high on research.
Germany also scores best in employment and job retention for people with multiple sclerosis, the barometer confirmed. This is due to protective legislation and flexible working conditions. 32% of people with MS are employed full time and 13% part time. An early retirement pension fund also exists.
Restricted access to care
At the same time, an EU country with low government spending on healthcare, like Poland, provides poorer treatment and quality of life for people with multiple sclerosis.
Poland has a very high ratio of people with multiple sclerosis, 120 in 100,000 people affected. Around 500 people are newly diagnosed each year. However, access to disease-modifying treatment provided is restricted. For example, after five years, access is transferred to the next person on the waiting list.
And though access to therapy for treating symptoms is relatively high, state reimbursement is modest with less than one-third of people having access to rehabilitation services.
Concerning employment, Poland fairs well due to strong laws against discrimination in the workplace. The country also scores well on empowerment of people with multiple sclerosis.
Lacking EU response
In September 2012, the European Parliament passed a written declaration initiated by the Romanian MEP Petru Luhan from the European People’s Party (EPP) on tackling multiple sclerosis in the EU, endorsed by more than 400 MEPs, calling for the European Commission and member states to enhance equal access to quality care.
But this commitment was not followed up with any concrete measures to reduce the inequalities for people with multiple sclerosis across the EU.
The EMSP said that the EU should live up to its declaration by addressing four major problems. First of all, the EU needs a closer scientific collaboration and comparative research on multiple sclerosis.
Secondly, there should be equal access to treatment and flexible employment policies for people with chronic neurological disorders such as multiple sclerosis.
Thirdly, there should be equal access to quality care, the EMSP said, for example by using certified educational training tools and lastly, collection of patient data at national level is encouraged in order to compare best practices.
EurActiv has asked Luhan as well as other MEPs, who have previously been involved with issues related to multiple sclerosis, for an interview. Unfortunately, they all declined.
Source: Euractiv © 1999-2014 EurActiv.com PLC (20/02/14)
Active Biotech today announces that its partner Teva Pharmaceuticals, has decided not to proceed to the randomization stage of the planned Libretto trial for the treatment of Relapsing Remitting Multiple Sclerosis (RRMS), as the current design is no longer aligned with the regulatory strategy. This decision has no impact on other ongoing studies, such as CONCERTO, which are proceeding as planned, or on Teva Pharmaceuticals' plans to initiate clinical studies in Primary Progressive Multiple Sclerosis (PPMS).
About laquinimod (Nerventra(R))
Laquinimod (Nerventra(R)) is an oral, investigational, CNS-active immunomodulator with a novel mechanism of action primarily being developed for the treatment of relapsing-remitting MS (RRMS). The global Phase III clinical development program evaluating oral laquinimod in MS includes two pivotal studies, ALLEGRO and BRAVO. A third Phase III laquinimod trial, CONCERTO, is evaluating two doses of the investigational product (0.6mg and 1.2mg) in approximately 1,800 patients for up to 24 months. The primary outcome measure will be time to confirmed disability progression as measured by the EDSS. In addition to the MS clinical studies, laquinimod has concluded Phase II of development for Crohn's disease and lupus nephritis.
Source: Market Watch Copyright © 2014 MarketWatch, Inc (19/02/14)
NICE Appraisal Committee has stated it cannot recommend oral MS drug Tecfidera.
Appraisal Committee's preliminary recommendations Tecfidera (dimethyl fumarate) for treating adults with relapsing–remitting multiple sclerosis.
- The Committee is minded not to recommend dimethyl fumarate within its marketing authorisation, that is, for treating adults with relapsing–remitting multiple sclerosis.
- The Committee recommends that NICE requests further clarification and analyses from the manufacturer, which should be made available for the second Appraisal Committee meeting, and should include the following:
Presentation of the results from the DEFINE and CONFIRM trials adjusted for baseline relapse rate only, for the following outcomes:
- proportion of patients with relapse at 2 years
- annualised relapse rate
- sustained disability progression confirmed for 3 months at 2 years
- sustained disability progression confirmed for 6 months at 2 years.
Revised probabilistic analyses incorporating a scenario that includes:
- revised mixed treatment comparison results adjusted for the baseline relapse rate
- revised estimates for monitoring resource use and costs as preferred by the Evidence Review Group (ERG) in its exploratory analyses
- a reduced cost of relapse estimate (£607.80) as preferred by the ERG in its exploratory analyses
- non-health costs are excluded (if non-health costs related to personal social services can be identified, these can be included), with a sensitivity analysis that includes all non-health costs, and
- pairwise comparisons and incremental analyses for the probabilistic cost-effectiveness estimates.
Pairwise comparisons for the probabilistic cost-effectiveness estimates for several plausible treatment sequences reflecting UK clinical practice. For example:
- dimethyl fumarate, beta interferon, fingolimod compared with beta interferon, glatiramer acetate, fingolimod
- dimethyl fumarate, beta interferon, glatiramer acetate compared with beta interferon, glatiramer acetate, fingolimod.
Pairwise comparisons for the probabilistic cost-effectiveness estimates for the current active treatments (all beta interferons and glatiramer acetate) compared with no disease-modifying therapy to externally validate the manufacturer’s economic model by showing how similar these cost effectiveness estimates are to those in the NHS risk-sharing scheme for multiple sclerosis.
Full Details on consultation & draft guidance.
Source: NICE (19/02/14)
Extensive renewal of the T cell repertoire following autologous stem cell transplant in MS(18/02/14)
A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.
In the Immune Tolerance Network's (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published today in the Journal of Clinical Investigation quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.
ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.
Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly comprised of new clones.
The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.
This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.
Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (18/02/14)
Differential effects of fingolimod on B-cell populations in multiple sclerosis
BACKGROUND: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells.
OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in patients with MS.
METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts.
RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38int-high), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138+) among whole plasmablasts, in the patients treated with fingolimod.
CONCLUSIONS: The marked reduction of Ki-67+ memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138+ plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.
Nakamura M, Matsuoka T, Chihara N, Miyake S, Sato W, Araki M, Okamoto T, Lin Y, Ogawa M, Murata M, Aranami T, Yamamura T.
Source: Mult Scler. 2014 Feb 13. & Pubmed PMID: 24526661 (18/02/14)
Innovative self-help method for MS patients developed by Poole Hospital therapists to be rolled-out nationwide(18/02/14)
An innovative self-help method for multiple sclerosis patients, developed by two Poole occupational therapists, is being rolled out across the country.
Poole Hospital therapists Alison Nock and Vicky Slingsby have created a self-management programme to help patients better understand and manage extreme tiredness.
The FACETS – Fatigue: Applying cognitive behavioural and energy effectiveness techniques to lifestyle – programme, developed with Bournemouth University clinical research unit, has seen patients report a significant reduction in their fatigue.
Considerable interest has been shown in it and it is now being rolled out across the country in partnership with the MS Society which funded the research, undertaken by university researchers including research fellow Dr Sarah Thomas.
Fatigue affects the majority of people with MS and can be one of the most debilitating symptoms of the condition.
The programme helps them see tiredness as normal and enables them to use available energy more effectively as well as encouraging alternative thinking styles.
Alison said: “The programme helps people with MS understand extreme tiredness better and manage it on a day-to-day level.
“It is also beneficial for patients as they can meet others with fatigue issues. Based on information giving and discussion, it is interactive so patients can learn from each other’s experiences.”
MS patients at Poole Hospital were among the first to benefit from the programme. Research has demonstrated that 40 per cent of participants who received FACETS in addition to their routine care had improved fatigue levels compared to 19 per cent who did not receive it.
Patient Janet King, who benefited said: “I feel better able not only to understand my situation but, perhaps more importantly, deploy tools and strategies to help me cope and maintain an improved quality of life.
“The programme was well run by Alison and Vicky, who were positive, empathetic, knowledgeable and always engaging. Every session proved very informative.”
* People interested in receiving FACETS should speak to their local healthcare professional who can contact the MS Society for information about training opportunities.
Source: Daily Echo © Copyright 2001-2014 Newsquest Media (Southern) Ltd (18/02/14)
New blood cells fight brain inflammation(17/02/14)
Hyperactivity of our immune system can cause a state of chronic inflammation. If chronic, the inflammation will affect our body and result in disease. In the devastating disease multiple sclerosis, hyperactivity of immune cells called T-cells induce chronic inflammation and degeneration of the brain. Researchers at BRIC, the University of Copenhagen, have identified a new type of regulatory blood cells that can combat such hyperactive T-cells in blood from patients with multiple sclerosis. By stimulating the regulatory blood cells, the researchers significantly decreased the level of brain inflammation and disease in a biological model.
The results are published in the journal Nature Medicine.
Molecule activate anti-inflammatory blood cells
The new blood cells belong to the group of our white blood cells called lymphocytes. The cells express a molecule called FoxA1 that the researchers found is responsible for the cells' development and suppressive functions.
"We knew that some unidentified blood cells were able to inhibit multiple sclerosis-like disease in mice and through gene analysis we found out, that these cells are a subset of our lymphocytes expressing the gene FoxA1. Importantly, when inserting FoxA1 into normal lymphocytes with gene therapy, we could change them to actively regulate inflammation and inhibit multiple sclerosis, explains associated professor Yawei Liu leading the experimental studies.
Activating own blood cells for treatment of disease
FoxA1 expressing lymphocytes were not known until now, and this is the first documentation of their importance in controlling multiple sclerosis. The number of people living with this devastating disease around the world has increased by 10 percent in the past five years to 2.5 million. It affects women twice more than men and no curing treatment exists. The research group headed by professor Shohreh Issazadeh-Navikas from BRIC examined blood of patients with multiple sclerosis, before and after two years of treatment with the drug interferon-beta. They found that patients who benefit from the treatment increase the number of this new blood cell type, which fight disease.
"From a therapeutic viewpoint, our findings are really interesting and we hope that they can help finding new treatment options for patients not benefiting from existing drugs, especially more chronic and progressive multiple sclerosis patients. In our model, we could activate lymphocytes by chemical stimulation and gene therapy, and we are curios whether this can be a new treatment strategy", says professor Shohreh Issazadeh-Navikas.
And this is exactly what the research group will focus on at next stage of their research. They have already started to test whether the new FoxA1-lymphocytes can prevent degradation of the nerve cell's myelin layer and brain degeneration in a model of progressive multiple sclerosis. Besides multiple sclerosis, knowledge on how to prevent chronic inflammation will also be valuable for other autoimmune diseases like type 1 diabetes, inflammatory bowel disease and rheumatoid arthritis, where inflammation is a major cause of the disease.
Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (17/02/14)
A new study provides evidence that obstructive sleep apnea (OSA) is highly prevalent in people with multiple sclerosis (MS), and it suggests that OSA may be a contributor to the fatigue that is one of the most common and debilitating symptoms of MS.
Results show that one-fifth of MS patients surveyed in a large tertiary MS practice carried a diagnosis of OSA, and more than half were found to have an elevated risk for OSA based on a validated screening tool. Further analysis showed that OSA risk was a significant predictor of fatigue severity, even after adjusting for potential confounders such as age, gender, body mass index (BMI), sleep duration and depression.
"OSA may be a highly prevalent and yet under-recognized contributor to fatigue in persons with MS," said lead author and principal investigator Tiffany J. Braley, MD, MS, an Assistant Professor of Neurology from the University of Michigan Multiple Sclerosis and Sleep Disorders Centers in Ann Arbor, Mich. "Our study suggests that clinicians should have a low threshold to evaluate MS patients for underlying sleep disturbances."
The study results appear in the Feb. 15 issue of the Journal of Clinical Sleep Medicine, which is published by the American Academy of Sleep Medicine.
"Obstructive sleep apnea is a chronic illness that can have a destructive impact on your health and quality of life," said American Academy of Sleep Medicine President Dr. M. Safwan Badr. "People with multiple sclerosis who are found to have a high risk of OSA should be referred to a board certified sleep medicine physician for a comprehensive sleep evaluation."
Braley and her colleagues, Benjamin M. Segal, MD (Director of the University of Michigan Multiple Sclerosis Center), and Ronald D. Chervin, MD, MS, (Director of the University of Michigan Sleep Disorders Center) studied 195 MS patients who completed a sleep questionnaire and four validated instruments designed to assess daytime sleepiness, fatigue severity, insomnia severity and OSA risk. Medical records also were accessed to examine clinical characteristics that may predict fatigue or OSA risk.
According to the authors, the cross-sectional design of the study did not allow for an examination of cause-and-effect relationships. However, the results suggest that a substantial portion of MS-related fatigue could be eliminated by the diagnosis and successful treatment of OSA in patients with MS.
The National Multiple Sclerosis Society (NMSS) estimates that approximately 400,000 people in the U.S. have MS, making it the most common disabling neurological disease of young adults.
The AASM reports that OSA is a common sleep disorder that affects up to seven percent of men and five percent of women. It involves repetitive episodes of complete or partial upper airway obstruction occurring during sleep despite an ongoing effort to breathe. The most effective treatment option for OSA is Continuous Positive Airway Pressure (CPAP) therapy, which helps to keep the airway open by providing a stream of air through a mask that is worn during sleep.
Source: Science Codex (17/02/14)
Understanding the human brain could provide the foundation to explore new ways to treat and eventually prevent diseases such as multiple sclerosis, Parkinson's or Alzheimer's disease, according to the European Brain Council (EBC).
The brain is at the centre of exciting but challenging new times in neuroscience research.
“We have already identified a lot of gaps in knowledge about treatments of brain diseases,” said Gordon Francis, head of the NeuroInflammation Clinical Science Unit within the NeuroScience Franchise at the Swiss pharmaceutical company Novartis.
Francis was addressing a conference on Friday (14 February) focusing on brain-related issues in Barcelona, Spain, which advocated for a "brain-political road map" under the motto 'Understanding the brain: Where are we in 2014?'
Among the challenges that scientists are looking into are the loss of brain tissues which for example occur at very early stages of multiple sclerosis and dealing with the changes of brain volume, said Frederik Barkhof, professor of Neuroradiology at the VU University Medical Centre in Amsterdam.
According to data by the European Multiple Sclerosis Platform, at least 600,000 people in Europe are affected by multiple sclerosis, an autoimmune disease of the central nervous system.
The crippling disease, which strikes the white matter of the brain and spinal cord and affects the rest of the nervous system, has far-reaching consequences for society as more than one million people are affected indirectly through their role as carers and family members, the EMPS said.
However, despite its importance, knowledge on how the brain works is still very limited. According to researchers, understanding the complex brain could provide the foundation to explore new ways to treat, cure and eventually prevent brain diseases such as multiple sclerosis, Parkinson's or Alzheimer's disease.
“We don't want this to be a race or competition against cancer, cardiovascular diseases or diabetes," Mary Baker, president of the European Brain Council, told EurActiv.
“But it is the brain that manages cancer, cardiovascular diseases and diabetes. The brain is a very special organ, we must take care of it," Baker added.
A disease like multiple sclerosis significantly impacts on the quality of life of patients and their families. For example, less than 50% of people with multiple sclerosis will be employed 10 years after receiving their diagnosis. About one-third of people will also need a wheelchair within 20 years of developing multiple sclerosis, according to data published by the Multiple Sclerosis Foundation.
“We try to mobilise the key actors, among them the European Commission's DG Research, on the need for innovation (with news drugs), but also on the social impact of multiple sclerosis," Baker stressed.
Economic and social costs of brain diseases
According to the EBC, the direct cost of healthcare related to brain diseases has increased from €386 billion in 2004 to €798 billion in 2010, measured across 30 European countries.
This means “more money is spent into brain diseases than cancer or cardiovascular diseases”, according to Baker.
The EBC wants to put the emphasis on the economic burden of brain diseases, in particular on multiple sclerosis. Up to 2.5 million people worldwide are affected by multiple sclerosis. It's more often younger people between between 20 and 40 who are diagnosed with multiple sclerosis, and women are diagnosed three times as often as men.
In the UK alone, the direct healthcare costs of brain diseases are estimated at 37% of the overall health budget which Baker called "an enormous amount of money, simply not sustainable”.
A part from the economic burden on society, a multiple sclerosis diagnosis can be devastating for the individual young adult who may be starting careers and making plans for the future. Early adulthood is also a time when young people may be pursuing higher education, making new relationships or considering starting a family.
“They are the brains of the future,” Baker said.
More attention to research
The EBC advocates for more and better funding for brain research, for example a combination of public and private sector resources. The EBC is currently working with the Commission's DG Research and the Innovative Medicines Initiative (IMI) on one of Europe's largest public-private initiatives aiming at speeding up the development of better and safer medicines. The second project, IMI2, has a budget of €3.45 billion.
"The attention paid to brain diseases is still relatively low when you compare it to cancer or diabetes. In order to raise awareness on multiple sclerosis, you need to make clear what the implications of the conditions are, what the impact they have for a condition like multiple sclerosis which hits people it their 20s. It has a huge impact," Alan Thompson, chair of the International Progressive MS Alliance, told EurActiv.
"The problem with the pharmaceutical industry is that people think they are just raising the profile in order to sell more drugs, but a combined approach should be better," he said.
According to a survey conducted in 124 countries by the Atlas of MS, access to drugs (Disease-Modifying Therapies, DMTs, or Symptomatic treatments) is very limited in low or medium-income parts of the world. Only 40% in developing countries have access as opposed to 90% in high-income countries.
“Unfortunately, inequalities remain," Thompson stated.
Source: EurActiv © 1999-2014 EurActiv.com PLC (17/02/14)
Multiple sclerosis shows a "striking" association with obesity at age 20 years that strongly interacts with genetic susceptibility, according to an analysis of data from two case-control studies that examined environmental and genetic risk factors for MS.
This relationship between adolescent obesity and MS is of the same magnitude as the separate associations between MS and carriage of the high-risk HLA-DRB1*15 allele, absence of the protective HLA-A*02 allele, and smoking, said Dr. Anna Karin Hedström of the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and her associates.
"The biological explanations for these interactions are far from clear, but the data open [the way] for mechanistically oriented studies," they said.
Three previous studies have suggested that obesity in early life may be linked to increased risk of developing MS later. Dr. Hedström and her colleagues examined this association using data from a Swedish population-based, case-control study and from a separate American case-control study.
In the Swedish study, 1,510 adults with incident MS who were treated at 40 clinics across the country during a 7-year period and 2,017 control subjects completed detailed questionnaires concerning environmental exposures and other factors. The controls were matched for age, sex, and area of residence, and all the participants gave blood samples for HLA typing.
The American study involved 937 white adults with prevalent MS who were members of a single large health maintenance organization covering northern California and 609 white control subjects matched for age, sex, and area of residence. All the participants completed computer-assisted telephone interviews regarding environmental exposures and lifestyle factors.
All the subjects in both studies reported what their heights and weights had been at age 20 years, from which the investigators calculated body mass index (BMI).
In both studies, participants whose BMI at age 20 years was 27 kg/m2 or greater showed an increased risk of developing MS later in life, compared with those whose BMI was 18.5-21 kg/m2. The odds ratios (ORs) were 2.2 for subjects in the Swedish study and 1.8 for those in the American study, Dr. Hedström and her associates said (Neurology 2014 [doi:10.1212/WNL.0000000000000203]).
Similarly, participants with a slightly lower but still above-normal BMI of 25-27 kg/m2 showed a modestly increased risk of developing MS later in life: The ORs were 1.4 in the Swedish study and 1.3 in the American study.
These ORs were unchanged when a sensitivity analysis was performed, including only the study subjects who had been genotyped.
Participants who carried the high-risk HLA-DRB1*15 gene, did not carry the protective HLA-A*02 gene, and had a BMI of 27 kg/ m2 or greater at age 20 years had an OR of 16.2 for developing later MS, compared with those who had none of those risk factors. In contrast, subjects who had the same HLA profile but had not been obese at age 20 years had an OR of only 5.1.
The investigators proposed that the low-grade chronic inflammation associated with obesity, together with obesity’s adverse effects on autoimmunity, may raise the risk of HLA-related activation of T cells that attack the CNS.
Both the Swedish and the American study were limited in that they were retrospective and relied on participants’ self-reports. In addition, Dr. Hedström and her associates modified the usual definition of obesity for the purposes of their study. The typical standard for obesity is a BMI of greater than 30 kg/m2, not greater than 27 kg/m2. However, the number of subjects at this level of BMI was too small in the Swedish cohort to allow accurate analysis, so the researchers combined the top two categories of BMI into one designation of "obese."
This study was supported by several private nonprofit foundations, the Swedish Research Council for Health, Working Life and Welfare, and the U.S. National Institute of Neurological Disorders and Stroke. Dr. Hedström and five of the other seven authors reported no financial conflicts of interest. One coauthor reported ties to numerous industry sources and one reported receiving research support from Swedish government agencies.
Causality not yet established
This study and other research linking obesity early in life with the later development of MS are observational and cannot establish causality, so we don’t yet know whether decreasing obesity with diet and exercise will lead to a decrease in the incidence of MS.
Nevertheless, these findings are concerning. “It is time to begin developing a targeted approach to prevent MS by improving common health behaviors, including body weight and smoking,” Dr. Marrie and Dr. Beck said.
People who are at high genetic risk can be readily identified by focusing HLA genotyping on the first-degree relatives of known MS patients, they added.
Dr. Marrie is in the departments of internal medicine and community health sciences at the University of Manitoba, Winnipeg. She has received funding from Sanofi-Aventis and Canadian governmental agencies and nonprofit organizations, including the MS Society of Canada and the MS Scientific Foundation. Dr. Beck is in the department of biostatistics and computational biology at the University of Rochester (N.Y.) Medical Center. Dr. Beck has received support from a variety of healthcare companies as well the U.S. Food and Drug Administration and the U.S. National Institutes of Health.
These remarks were taken from their editorial accompanying Dr. Hedström’s report (Neurology 2014 [doi:10.1212/WNL.0000000000000195]).
Source: Clinical Endocrinology New Copyright © 2014 Frontline Medical Communications LLC (12/02/14)
Multiple Sclerosis is an autoimmune disease that affects the brain and spinal cord, destroying tissue and cells along the way. Previous research and practices have found that therapies can help with relapses of MS, but cannot help repair the tissue and cells that have been affected.
After MS has affected the body and caused cell damage, the brain produces new cells to repair the old ones. However, a majority of cases has shown that there are unknown factors that hinder the cells from completely repairing, thus creating a permanent loss. The brain inflammation caused by MS leads to the destruction of myelin, which is the fatty insulation for the axon nerve fibers in the brain, thus destroying brain cells. A molecule known as Endothelin-1 (ET-1) is known to inhibit the repair of the myelin.
Yesterday, Gallo and his team of researchers reported their findings in Neuron and cited the effectiveness of a certain protein that could help fully repair previously damaged cells. This protein, known as "ET-R antagonist PD142,893" can be used therapeutically to promote remyelination and effectively block ET-1 from inhibiting cell repair.
"We demonstrate that ET-1 drastically reduces the rate of remyelination," Gallo said. "ET-1 is potentially a therapeutic target to promote lesion repair in deymyelinated tissue. It could play a crucial role in preventing normal myelination in MS and in other demyelinating diseases," Gallo said.
Source: Science World Report (10/02/14)
Scientists recently uncovered a key finding that CD4 T cells are not involved with Multiple Sclerosis progression after recent trials revealed that a depleting CD4-specific antibody failed to affect MS. The question is: did the depleting CD4 specific antibody fail to affect MS, or was the experimental design flawed? Essentially, immunologists claim that CD4 cells are at the center of the immunological research world simply because they are involved with other aspects of immune responses in order to be able to do what they do.
Zastepa et al., (Neurology Jan. 2014) have looked at whether altered naïve CD4 T-cell biology contributes to development of disease progression in secondary progressive multiple sclerosis (SPMS). The researchers were able to compare naïve CD4 T-cell gene expression profiles of 19 patients with SPMS vs 14 healthy controls using a whole-genome microarray approach. They looked at surface protein expression of critical genes by flow cytometry after T-cell receptor (TCR) activation of naïve CD4 T cells isolated from healthy controls and patients with SPMS.
The researchers separated patients with SPMS into two subgroups: SP-1, which had a short duration of relapsing-remitting MS, and SP-2, which had a long duration of relapsing-remitting MS. They discovered that SP-1 patients upregulated many immune genes, within the TCR and toll-like receptor (TLR) signaling pathways. SP-2 patients demonstrated down regulation of immune genes in comparison with healthy controls. They also found an SP-1-specific transcriptional signature of 3 genes which includes TLR4, TLR2 and chemokine receptor 1. These genes had a higher surface protein expression in SP-1 than SP-2. After researchers stimulated TCR for 2 days, only SP-1 showed a progressive linear increase in TLR2 and TLR4 protein expression.
The researchers suggest that changes in naïve CD4-T-cell biology, particularly that of TCR and TLR signaling pathways, identify MS patients with a rapid conversion to secondary progression. This is important because this identifies long-term disability in MS. In fact, certain proteins are in higher concentration on T cells from progressive MS patients that progress faster. What are these proteins doing you ask? That is not known as this time, however Toll-like receptors involved with microbe recognition and infections are important to the rate of progression. We know that blocking CD4 activity doesn’t stop progression, but the question is whether it changes the slope (rate of change). We expect to find this answer from the SP1 and tysabri trials.
Source: BioNews Texas (06/02/14)
Life-changing MS treatment shows promise(05/02/14)
Australian scientists are showing promising results with a new treatment for advanced multiple sclerosis (MS).
It's early days, but it has changed the life of Dr Gary Allen, a 43-year-old academic with secondary progressive MS who agreed to be a guinea pig.
He was given six weeks of treatment, which resulted in a sustained boost of energy, reduced pain and increased productivity at work.
"It's impossible to overstate the improvements," said Dr Allen.
The study on the treatment is a high point in the career of Professor Michael Pender, who has been researching MS for 33 years.
In 2003 he proposed a new theory that people with MS have impaired immunity to Epstein-Barr virus (EBV).
There is a growing body of evidence to support his view that this allows the virus to accumulate in the brain and cause MS.
EBV is a well known as a cause of glandular fever.
The new treatment boosts the body's ability to fight the virus, said Prof Pender, of The University of Queensland.
"EBV gets out of control in the brain of MS patients.
"Our study shows that controlling it can stop the disease from getting worse and allow some recovery of function," said Prof Pender, who worked with Professor Rajiv Khanna of the QIMR Berghofer institute to develop the treatment.
Dr Allen, who has been unable to walk since 2008, said his concentration, memory, hand function and leg movement had improved during the treatment.
There has also been reduced disease activity on brain scans and a reduction in antibodies in his spinal fluid.
"Whether you look at my work, time with my family or social life, it's been an amazing change for the better," said Dr Allen.
Dr Matthew Miles, Chief Executive of MS Research Australia, said he was delighted with the study.
"This has profound implications globally for understanding the cause and treatment of MS, particularly in its progressive phase."
A report on the treatment is published in the latest issue of the Multiple Sclerosis Journal.
Source: Herald Sun Copyright News Ltd 2014 (05/02/14)
Genzyme, a Sanofi company, announced today that Mexico's national regulatory authority, COFEPRIS, has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing remitting forms of multiple sclerosis (MS) to slow or reverse the accumulation of physical disability and reduce the frequency of clinical exacerbations.
"The approval of Lemtrada in Mexico is an important step forward for MS patients, who remain in great need of new treatment options that may offer greater efficacy," said Miguel A. Macias, M.D., Department of Neuroscience, University of Guadalajara. "The positive effect on disability progression demonstrated in clinical studies underscores Lemtrada's ability to address the course of disease in a potentially transformative way for patients with relapsing remitting MS."
Lemtrada is supported by a comprehensive and extensive clinical development program that involved nearly 1,500 patients and 5,400 patient-years of follow-up. Approval in Mexico follows the recent approvals of Lemtrada in Canada, Australia and the European Union. Lemtrada is currently not approved in the United States. In December, Genzyme received a complete response letter from the FDA on its application for U.S. approval of Lemtrada. Genzyme plans to appeal the agency's decision. Marketing applications for Lemtrada are also under review in other countries.
More than 2.5 million people worldwide have been diagnosed with MS, including approximately 15,000 people in Mexico. Lemtrada has been granted orphan drug designation in Mexico.
Lemtrada 12 mg has a novel dosing and administration schedule of two annual treatment courses. The first treatment course of Lemtrada is administered via intravenous infusion on five consecutive days, and the second course is administered on three consecutive days, 12 months later.
"The approvals in the European Union, Australia, Canada and now Mexico underscore Lemtrada's potential to have a positive impact on the lives of MS patients," said Genzyme President and CEO, David Meeker. "Genzyme remains committed to providing new hope for the MS community and plans this year to launch Lemtrada in more than 30 countries, and hopefully additional markets where the treatment is still under review."
The Lemtrada clinical development program included two randomized Phase III studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif(R) ) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II), as well as an ongoing extension study. In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.
The most common side effects of Lemtrada are infusion associated reactions, infections (upper respiratory tract and urinary tract), lymphopenia and leukopenia. Autoimmune conditions and serious infections can occur in patients receiving Lemtrada. A comprehensive risk management program incorporating education and monitoring will support early detection and management of these identified risks.
Source: Wall Street Journal Copyright ©2014 Dow Jones & Company, Inc (04/02/14)
Oral MS drug Tecfidera® (Dimethyl Fumarate) approved in the European Union Tecfidera® (dimethyl fumarate) has been approved by the European Commission (EC) as a first-line oral treatment for people with relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis (MS). Biogen Idec will begin to introduce Tecfidera in initial European Union (EU) countries in the coming weeks.
Tecfidera was first approved in the United States in March 2013 and became the country’s number one prescribed oral therapy for relapsing forms of MS after six months.1 Tecfidera was also approved in Canada and in Australia in 2013.
“Tecfidera exemplifies our commitment to deliver innovative therapies that help people living with serious diseases,” said George A. Scangos, Ph.D., chief executive officer of Biogen Idec. “We already have seen Tecfidera’s significant impact on transforming the standard of care for MS where it is available and are excited to quickly bring its benefits to patients in the EU as well.”
The EC approval is based on a robust clinical development program that included two global Phase 3 clinical trials, DEFINE and CONFIRM, as well as an ongoing extension study, ENDORSE, in which some patients have been followed for up to six and a half years. Tecfidera has been clinically shown to significantly reduce important measures of disease activity, including relapses and the development of brain lesions, as well as to slow disability progression, while demonstrating a favourable safety and tolerability profile.
“As a physician, I am all too familiar with the challenges my patients experience while managing their MS. Tecfidera may lower this burden for many because it is an oral therapy that has been proven to lessen disease activity effectively while maintaining a favorable safety profile,” said Ralf Gold, M.D., professor and chair of the Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum and lead investigator of DEFINE. “Moreover, the positive experience we have had with Tecfidera throughout its extensive clinical program gives me confidence about the benefits this oral therapy may offer my patients in the EU.”
Source: MarketWatch Copyright © 2014 MarketWatch, Inc (03/02/14)
Researchers at Kessler Foundation have studied the measurement tools used in multiple sclerosis for their effectiveness in predicting employment status. They compared the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Functional Composite (MSFC), the Paced Auditory Serial Addition Task (PASAT), and the Symbol Digit Modalities Test (SDMT), and found the SDMT effective in differentiating employed from unemployed individuals. The article, Unemployment in multiple sclerosis (MS): utility of the MS Functional Composite and cognitive testing, was published in the January 2014 issue of Multiple Sclerosis Journal (doi: 10.1177/1352458513488235). The authors are Lauren Strober, PhD, Nancy Chiaravalloti, PhD, Nancy Moore, PhD, and John DeLuca, PhD, of Kessler Foundation.
"The population with MS comprises people of working age," noted Dr. Strober, senior research scientist, "which is why factors related to employment status are a major concern for individuals and clinicians." The researchers studied 77 people with MS; 40 were employed and 37 were unemployed. To determine which factor(s) were predictive of employment status, they compared the two groups in regard to demographic factors, disease variables, MSFC, and cognitive performance. Differences were found in disease duration and progression, upper extremity function, processing speed, verbal learning and memory, and executive function. Analysis revealed the SDMT to be the only predictor of employment status, with an overall accuracy of 67%. "These findings suggest that clinical use of the SDMT may help identify those individuals who are at risk for unemployment," she explained. "This would allow clinicians to advise them on strategies for maintaining employment."
"Unemployment research is a priority at Kessler Foundation," remarked Dr. Chiaravalloti, "because maintaining employment is such an important factor in the quality of life of persons with MS."
Source: News Medical (03/02/14)
A recently completed study at University College London Hospital suggests that administration of certain drugs can block the entry of sodium ions in nerve cells that in turn can prevent aggressive nerve cell damage. The research team proposed that delaying nerve cell destruction can limit the rate of disability in secondary progressive MS patients. The supporting study, which was completed after two years of testing, was aimed at employing nerve cell blockers like lamotrigine to monitor the rate of worsening disability in secondary progressive MS patients.
The Primary Outcome of this double-blind interventional study was to monitor changes in the volume of the whole brain with the help of the Loseff method using MRI technology (to monitor cerebral atrophy due to loss of axons). Secondary Outcomes for the study included monitoring the changes in the volume of whole brain with the help of Brain Boundary Shift Integral; the rate of atrophic changes in the spinal cord; appearance of new high intensity lesions on an MRI scan; ratio calculation of new T1 and T2 lesions; and the overall rate of changes in the MS Functional Composite and Impact Scale.
The cerebral and spinal volumes and cross-sectional area of the cervical spinal cord were tested at baseline, at 12 months into the study, and towards the end of the study period (24th month). Brain volume was measured more periodically at the 6th and 18 month marks, as well as at the 12 and 24 month marks. The clinical visits were planned for every 3 months.
Details of the Study:
The research team enrolled 120 patients with a positive history of MS and a progressive course of illness as seen in secondary progressive MS patients (patients with frequent episodes of clinical relapses resulting in disability were excluded). The study sample was divided into a test group and control groups, and the patients were randomly selected to receive either placebo or lamotrigine.
The research team explained that degenerative spinal or cerebral diseases can respond fairly well to neuroprotective treatments. The cause of disease progression in multiple sclerosis is degeneration of nerve axons. Previous research projects conducted by investigators at the University College London Hospitals have concluded that inflammatory mediators like nitric oxide can contribute to axonal degeneration. Various in-vitro studies confirm that blocking the activity of sodium channels can reduce the degeneration of axonal processes. Several pharmacological agents are currently available that are used to block sodium channels in the brain tissue (like phenytoin and flecainide in addition to lamotrigine).
Positive results from the Phase 2 clinical trial will pave the way for Phase 3 clinical trials and also confirm the neuroprotective role of sodium channel blockers in the nerve cell disorders, like secondary progressive MS, to limit the rate of complications and long-term disability.
Lamotrigine is a sodium channel blocker that is widely prescribed for the management of epilepsy and seizure disorders under the brand name of Lamictal XR. Other indications for lamotrigine use are bipolar disorders, mood disorders, attention deficit hyperactivity disorder, and sleep disorders. Like all anti-conculsants, it is also associated with dose-dependent side-effects and is therefore sold as a prescription drug in most parts of the world.
Source: BioNews Texas (03/02/14)