Daily News for Neuros, Nurses & Savvy MSers: 208,152 Viewers, 8,368 Stories & Studies
Click Here For My Videos, Advice, Tips, Studies and Trials.
Timothy L. Vollmer, MD
Department of Neurology
University of Colorado Health Sciences Center Professor

Co-Director of the RMMSC at Anschutz Medical Center

Medical Director-Rocky Mountain MS Center
Click here to read my columns
Brian R. Apatoff, MD, PhD
Multiple Sclerosis Institute
Center for Neurological Disorders

Associate Professor Neurology and Neuroscience,

Weill Medical College of Cornell University

Clinical Attending in Neurology,
New York-Presbyterian Hospital
You'll get FREE Breaking News Alerts on new MS treatments as they are approved

HERE'S A FEW OF OUR 6000+ Facebook & MySpace FRIENDS
Timothy L. Vollmer M.D.
Department of Neurology
University of Colorado Health Sciences Center
Co-Director of the RMMSC at Anschutz Medical Center
Medical Director-Rocky Mountain MS Center

Click to view 1280 MS Walk photos!

"MS Can Not
Rob You of Joy"
"I'm an Mom has MS and we have a message for everyone."
- Jennifer Hartmark-Hill MD
Beverly Dean

"I've had MS for 2 years...this is the most important advice you'll ever hear."
"This is how I give myself a painless injection."
Heather Johnson

"A helpful tip for newly diagnosed MS patients."
"Important advice on choosing MS medication "
Joyce Moore

This page is powered by Blogger. Isn't yours?




It is one of 4,613 stories on our MySpace Blog!

Our 3,300 MySpace Friends have made 29,896 Comments & 42,234 Kudos on the 4,613 stories!


FDA Approves Tapentadol Immediate-Release Tablets for Relief of Moderate to Severe Acute Pain...[CLICK HERE FOR FULL PRESS RELEASE]

Raritan, NJ - Millions of Americans with moderate to severe acute pain and their health-care providers will soon have a new treatment option. Today, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., (J&JPRD), announced that the U.S. Food and Drug Administration (FDA) approved tapentadol immediate-release tablets for the relief of moderate to severe acute pain in adults 18 years of age or older.

Tapentadol is a new centrally acting oral analgesic. It has two mechanisms of action, combining mu-opioid receptor agonism and norepinephrine reuptake inhibition.

Tapentadol tablets have been approved in 50 mg, 75 mg and 100 mg doses.

The approval was based .. from clinical studies involving more than 2,100 patients. The studies, which were presented at the 27th Annual Scientific Meeting of the American Pain Society earlier this year, showed that tapentadol provided significant relief of moderate to severe acute pain compared to placebo.

Following today's FDA approval, and as per Federal regulation for all controlled substances, tapentadol will be reviewed by the U.S. Drug Enforcement Agency for scheduling, and it cannot be sold until it receives a scheduling classification.

A trade name for tapentadol has not yet been determined.

"We are pleased with the FDA's approval today. Tapentadol represents a new treatment option in pain management, and I am excited that we are able to bring this new choice to patients who are suffering from pain," said Joanne Waldstreicher, M.D., Global Head, Research and Development for CNS/Internal Medicine, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

More than 25 million Americans experience acute pain each year as a result of injuries or surgery, and it is the most common reason people seek medical attention.

"We welcome new proven treatment options that can help people with pain," said Mark Rasmussen, President/CEO, The National Pain Foundation, Denver, CO.

PriCara®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., will market tapentadol in the United States. J&JPRD and Ortho-McNeil-Janssen Pharmaceuticals, Inc. are wholly owned subsidiaries of Johnson & Johnson.

Approval Based on Results of Phase 3 Studies
Multiple Phase 3 studies presented at the 27th Annual Scientific Meeting of the American Pain Society in May showed tapentadol offers patients significant relief of their pain when compared to placebo, and that the medicine was generally well tolerated in these studies.

The studies were conducted in different patient groups, including those who had a bunionectomy, a standard foot surgery associated with predictable levels of moderate to severe pain, and in those with pain from end-stage joint disease.

At the same meeting, a Phase 3 safety study of tapentadol immediate-release tablets was presented. This study evaluated tapentadol in patients with low back pain or pain from osteoarthritis of the hip or knee. It demonstrated that tapentadol offers pain relief and is generally well tolerated. (

Two Mechanisms of Action
Mu-opioid agonists are drugs that bind to and activate mu-opioid receptors in the central nervous system. These drugs modify sensory and affective aspects of pain, inhibit the transmission of pain at the spinal cord and affect activity at parts of the brain that control how pain is perceived. Norepinephrine reuptake inhibitors are a type of central nervous system medication that increases the level of norepinephrine in the brain by inhibiting its re-absorption into nerve cells; these compounds have analgesic properties.



Helping the disabled or elderly walk with care

A new Israeli device the ReWalk -- worn like an exoskeleton and maneuvered with crutches -- promises to give mobility to paraplegics. The company developing it, Argo Medical Technologies, has made news that has circled the globe.

Hot on its heels is Walk-Care. Inspired by the late Christopher Reeve's visit to Israel in 2003, Walk-Care's two founders, a gemologist and an aeronautics engineer, have paired up to revolutionize the "transportation" market for the disabled.

But really, their primary motive, says CEO Jacob Gabel is to change the lives of people with motor movement disabilities, and to do it at a cost most people can afford. "We spent two years talking to rehabilitation center specialists around Israel asking them for a wish-list -- what they would like in such a device for their patients," Gabel, the engineer, and a retired Israeli Air Force colonel tells ISRAEL21c. "

Without daily exercise, muscle mass withers away, circulation slows down and a whole set of new complications arise, such as osteoporosis and bedsores, which can lead to infection and death.

Walk with tears of joy

One success story is a woman who recently tried out the Walk-Care prototype, still heavily guarded until funding is secured to take the device from prototype stage to market. The 42-year-old woman hadn't used her legs for 30 years. " With Walk-Care, she was walking on her own feet again," says Gabel. There were lots of tears.

One of the big failures of other devices, he points out, is the embarrassment factor. With high rates of failure, it's far too common for a disabled person, especially the more severe ones, to topple over when using an assisted walking device.

Rehab doctors "go ballistic" over new device

Not ready to release images, Gabel says that top rehabilitation doctors in Israel have tried it out, exclaiming that it's a dream come true. "They went to the machine and used it on themselves and they went ballistic," says Gabel.

For the price of a small car -- about $15,000 -- the Walk-Care device comes highly customizable, meaning it can be operated with buttons, voice commands, or even with a blow straw, depending on the disability. It can even ride over uneven and bumpy surfaces such as grass.

The user literally walks on his own feet, and this is the whole point," says Gabel, emphasizing the importance of moving the legs for circulation and health. It's also essential, he tells ISRAEL21c, that the disabled get the opportunity to interact in this world on the same level as fully mobile people. Both for peace of mind and for building a life others take for granted.


Exploring the Relationship Between Sleep and Pain

Disturbed sleep is a common comorbidity of patients who experience pain. Between 50% and 88% of patients with chronic pain also demonstrate sleep disturbances.
Medscape Today


New Approaches to the Pharmacotherapy of Neuropathic Pain

Pain is one of the most debilitating symptoms that presents with neuropathy. Neuropathic pain syndrome is a challenge to treat and, even with appropriate evidence-based treatment, only a 40% reduction of symptoms can be achieved in approximately half of patients.
MedScape Today


Fatigue characteristics in multiple sclerosis: the North American Research Committee on Multiple Sclerosis (NARCOMS) survey.

Characterizing MS symptoms like fatigue can increase awareness about their impact on persons with MS and suggest recommendations for a care plan.
Health Qual Life Outcomes, November 14, 2008; 6(1): 100.
HighWire Press Stanford University


Assessment of Mitoxantrone-Induced Cardiotoxicity in Patients with Multiple Sclerosis: A Tissue Doppler Echocardiographic Analysis.

Tissue Doppler echocardiography was investigated for its applicability in detecting subtle myocardial involvement in multiple sclerosis patients receiving a low dose of mitoxantrone.
Echocardiography, November 1, 2008; .
Highwire Press Stanford University


Eval. of the Safety and Efficacy of Sildenafil Citrate for Erectile Dysfunction in Men With MS A Double-Blind, Placebo Controlled Randomized Study

We evaluated the safety and efficacy of sildenafil citrate for treating erectile dysfunction in patients with multiple sclerosis.
J Urol, November 13, 2008;
Highwire Press Stanford University


Review Article: MS Reproductive Risks in Women.

Current knowledge shows that women with MS are no more likely to have pregnancy or delivery complications compared to healthy women.
Reproductive Sciences, October 1, 2008; 15(8): 755-764.
Highwire Press Stanford University


Pregnancy and multiple sclerosis.

This article aims to provide a brief overview for the general neurologist of the most commonly encountered issues and questions including those occasionally related to pregnancy management. The take-home message is that pregnancy does not hold adverse risks for the majority of patients with MS, or vice versa.
J. Neurol. Neurosurg. Psychiatry, December 1, 2008; 79(12): 1308-11
Highwire Press Stanford University



Multiple sclerosis and the TNFRSF1A R92Q mutation

We recommend careful observation of MS patients with coexisting TRAPS with regard to unexpected side effects of immunomodulatory therapies.
NEUROLOGY 2008;71:1812-1820


Excessive acute migraine medication use and migraine progression

Long considered a chronic disorder with a stable course, recent research demonstrates that, in a subgroup, migraine progresses to chronic migraine. Among the risk factors for migraine progression, acute symptomatic medication overuse (SMO) is regarded as one of the most important.
NEUROLOGY 2008;71:1821-1828



Relapsing-Remitting Multiple Sclerosis - Teva Completes Enrollment In Laquinimod Phase III Clinical Trial

Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) and Active Biotech (NASDAQ OMX NORDIC: ACTI) today announced completion of patient enrollment for the Phase III clinical trial, Allegro, in relapsing-remitting multiple sclerosis (RRMS). The pivotal Allegro study is designed to evaluate the efficacy, safety and tolerability of the oral investigational compound, laquinimod, versus placebo in the treatment of RRMS.

The Allegro study completed patient screening at the end of the third quarter. Recruitment of over 1,000 patients at 152 sites throughout North America, Europe and Asia was finalized in November. The completion of recruitment triggers a milestone payment of $5 million to Active Biotech from Teva Pharmaceutical Industries Ltd.

A second pivotal Phase III clinical trial evaluating laquinimod, called Bravo, is currently enrolling patients globally. The Bravo trial aims to provide risk-benefit data for laquinimod versus Avonex®, an available injectable treatment. Previous data from the phase IIb core study and its 36-week extension period (presented at the World Congress on Treatment and Research in MS in September) demonstrated the rapid onset and sustained efficacy of laquinimod in reducing disease activity, as well as the favorable safety profile of the compound.
Medical News Today



News Keeps Getting Worse for Vitamins

The best efforts of the scientific community to prove the health benefits of vitamins keep falling short.

This week, researchers reported the disappointing results from a large clinical trial of almost 15,000 male doctors taking vitamins E and C for a decade. The study showed no meaningful effect on cancer rates. Another recent study found no benefit of vitamins E and C for heart disease.

In October, a major trial studying whether vitamin E and selenium could lower a man’s risk for prostate cancer ended amidst worries that the treatments may do more harm than good.

And recently, doctors at Memorial Sloan-Kettering Cancer Center in New York warned that vitamin C seems to protect not just healthy cells but cancer cells, too.

Everyone needs vitamins, which are critical for the body. But for most people, the micronutrients we get from foods usually are adequate to prevent vitamin deficiency, which is rare in the United States. That said, some extra vitamins have proven benefits, such as vitamin B12 supplements for the elderly and folic acid for women of child-bearing age. And calcium and vitamin D in women over 65 appear to protect bone health.

But many people gobble down large doses of vitamins believing that they boost the body’s ability to mop up damaging free radicals that lead to cancer and heart disease. In addition to the more recent research, several reports in recent years have challenged the notion that megadoses of vitamins are good for you.

Despite a lack of evidence that vitamins actually work, consumers appear largely unwilling to give them up. Many readers of the Well blog say the problem is not the vitamin but poorly designed studies that use the wrong type of vitamin, setting the vitamin up to fail. Industry groups such as the Council for Responsible Nutrition also say the research isn’t well designed to detect benefits in healthy vitamin users.



Social anxiety in a multiple sclerosis clinic population

Social anxiety symptoms are common in persons with MS, contribute to overall morbidity, but are unrelated to the overall severity of neurologic disability. Greater awareness and routine systematic inquiry of social anxiety symptoms is an important component of comprehensive care for persons with MS.
Sage Journals Online


Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients MS

It is unknown whether immunosuppression of patients who have developed interferon- (IFN-) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood.
Sage Journals Online


An APOA1 promoter polymorphism is associated with cognitive performance in patients with multiple sclerosis

Elevated ApoA1 levels have been associated with decreased dementia risk. The A-allele of the APOA1 –75G/A promoter polymorphism has been associated with elevated ApoA1 levels.
Sage Journals Online


Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with MS for detection of JC virus DNA

To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML).
Sage Journals Online

Labels: ,


Switching first-line disease-modifying therapy after failure: impact on the course of RR-MS

Options for non-responders to relapsing–remitting multiple sclerosis (RRMS) first-line disease-modifying therapies (DMT) are limited. We explored whether switching first-line DMT is effective.
Sage Journals Online


Outcome measures for trials of remyelinating agents in MS: retrospective longitudinal analysis of visual evoked potential latency

Visual evoked potentials (VEP) may be suitable surrogate outcome measures in multiple sclerosis (MS) remyelination trials. The extent of spontaneous changes of subclinically delayed VEP is unknown, whereas VEP improve after acute optic neuritis (ON).
Sage Journals Online


Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of MS only in women

Multiple sclerosis (MS) is a chronic inflammatory disease with an as yet not fully understood etiological background. The geographical distribution of MS is striking with a prevalence that increases with latitude. For this reason, vitamin D deficiency is considered a possible pathogenic co-factor in MS.
Sage Journals Online


Use of health services in people with multiple sclerosis with and without fatigue

To explore and compare the use of health services in people with multiple sclerosis (MS) with and without fatigue.
Sage Journals Online


Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of MS

To date, there is no reliable method by which to characterize the immune processes and their changes associated with different forms of MS and disease progression. We performed antigen microarray analysis to characterize patterns of antibody reactivity in MS serum against a panel of CNS protein and lipid autoantigens and heat shock proteins.
PNAS - Proceedings of the National Academy of Sciences


Interferon- bioactivity measurement in multiple sclerosis: feasibility for routine clinical practice

Neutralising antibodies (NAb) to interferon beta (IFN) are associated with a reduced bioactivity and efficacy of IFN in multiple sclerosis (MS). Unclear is how to apply IFN bioactivity measurements (quantification of Myxovirus resistance protein A (MxA) mRNA) in clinical practice
Sage Journals Online


Head injury is not a risk factor for multiple sclerosis: a prospective cohort study

To determine whether head trauma is associated with an increased risk of developing MS.
Sage Journals Online


Tried and tested: the psychometric properties of the MS impact scale (MSIS-29) in a population-based study

To investigate the psychometric properties of the Multiple Sclerosis Impact Scale (MSIS-29) and to assess the relationship between the Kurtzke Expanded Disability Status Scale and the physical and psychological parts of this score.
Sage Journals Online



Measuring adherence and persistence to disease-modifying agents among patients with relapsing remitting MS..

To measure disease-modifying agent adherence and persistence among patients with multiple sclerosis (MS).
J Am Pharm Assoc (2003). 2008 November-December 1;48(6):752-757.



Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in MS

J Intern Med. 2008 Oct 25. [Epub ahead of print]



Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features.

The aim of this study was to compare the characteristics of the first demyelinating event between acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS).
Dev Med Child Neurol. 2008 Oct 23. [Epub ahead of print]



Cuprizone treatment induces demyelination and astrocytosis in the mouse hippocampus.

Memory impairment is outstanding within the spectrum of cognitive deficits in multiple sclerosis (MS) patients. Demyelination has been reported in the hippocampus formation of MS patients.
J Neurosci Res. 2008 Nov 19. [Epub ahead of print]



Review Article: Multiple Sclerosis and Reproductive Risks in Women.

During the previous decades, women with Multiple Sclerosis (MS) were discouraged from having children, as pregnancy was deemed dangerous for pregnancy outcome and a contributing factor for exacerbation of MS.
Reprod Sci. 2008 Oct;15(8):755-764.



Impact of fluoxetine on the human brain in multiple sclerosis as quantified by proton magnetic resonance spectroscopy and diffusion tensor imaging.

The antidepressant fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. In multiple sclerosis patients fluoxetine administration may improve energy supply in neuron cells and thus inhibit axonal degeneration.
Psychiatry Res. 2008 Nov 17. [Epub ahead of print]



Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early MS.

Therapeutic targeting of the identified mechanisms of tissue injury might be crucial to prevent further lesion formation or secondary tissue damage.
Brain Pathol. 2008 Oct 31. [Epub ahead of print]



Disease-Modifying Agents for MS: Recent Advances and Future Prospects.

Currently, six medications are approved for immunmodulatory and immunosuppressive treatment of the relapsing disease course and secondary-progressive MS. In the first part of this review, the pathogenesis of MS and its current treatment options are discussed.
Drugs. 2008;68(17):2445-2468. doi: 10.2165/0003495-200868170-00004.



`Unprecedented' Biotech Bankruptcies Erupt Amid Finance Crisis

Nov. 21 (Bloomberg) -- The global economic crisis has cut funding for biotechnology companies to the lowest level in a decade, triggering bankruptcies and threatening development of drugs based on biomedical breakthroughs.

In the past month, at least five biotechnology businesses have sought bankruptcy protection, according to company news releases, and others may be heading toward a similar fate. Those at highest risk have experimental compounds moving into costly human research. Peptimmune Inc., a 6-year-old closely held firm, says it’s struggling to pay for clinical trials of its promising multiple sclerosis drug.

The amount raised this year by biotechnology companies fell by $9.7 billion through September, or 54 percent, compared with the same period in 2007, according to Burrill & Co., a life sciences investment bank in San Francisco. That may mean work on dozens of potential treatments will stall or die as companies fire workers and shelve early research projects, industry executives and investors said.

“For the first time in the history of the biotech industry, you’re going to see unprecedented levels of bankruptcies and dissolutions,” said David Strupp, managing director in the life sciences group at Canaccord Adams, a research and investment bank in New York. “This all will play out in the next six to nine months.”

Most Advanced Drug

Peptimmune’s most advanced drug, PI-2301, is a multiple sclerosis treatment designed to be taken weekly. It would compete with Teva Pharmaceutical Industries Ltd.’s daily treatment Copaxone, which generated $1.7 billion in sales last year. Peptimmune is counting on positive data from a study due in 2009 to show its drug is better than Copaxone.

“If the multiple sclerosis program doesn’t do well, it will be very difficult for this company to raise money,” Mathers said.

Peptimmune, with no products on the market, has raised and spent about $85 million. Biotech companies without products on the market, or those unable to access equity markets by selling shares, are the ones in most need of cash to fund clinical studies, investors and company executives said.

“We’re at a stage that a lot of companies are in, where it’s time to raise money but there’s no clinical data and you’re not a brand new company coming out of academia,” Andrews said. “I suspect there will be a number of companies that will go down this path.”




New Device Helps Patients

For one woman suffering with Multiple Sclerosis, walking was impossible until she found a new medical device.

For years she struggled as the disease progressed, and eventually she lost the ability to move around without help.

"My sister had bought me a scooter, and I was using the scooter probably 80 percent of my life. I couldn't walk," Delsie said.

Now 15 years after her diagnosis, a new device has changed her life. The Bioness l300 attaches to her knee and ankle.

"It has electrodes placed on the inside and it sends electrical impulse to the muscle. For the first time I can walk into buildings, and it's opened a whole new door. I am mobile again."

The device helps her lift her foot, and keeps her posture straight. She controls the impulses herself and physical therapy helps her learn to coordinate the movements.

"It's been a lot of work but with each day a new advancement and it's become easier and easier and now I can walk. It changes lives, it really does. I can walk."




Weight Loss Surgery Helps Obese Women Have Healthier Babies

Women who become pregnant after weight-loss surgery have easier pregnancies and healthier babies than do obese women who become pregnant, researchers reported on Wednesday.

With more than 50,000 young women having bariatric surgery each year, Dr. Maggard added, continued research on the effects of weight loss surgery is needed.

About one-third of American women are obese, and doctors usually encourage them to lose weight before becoming pregnant. Obese women are at greater risk for developing pregnancy-related health problems; their babies are more likely to be born prematurely, stillborn, to be very large or to have a neural tube defect.

Fertility seemed to improve after surgery as hormone levels and menstrual cycles returned to normal following weight loss, the review found. In some earlier studies, polycystic ovarian syndrome had resolved or improved after weight loss as well, the authors noted.

The most serious complications during pregnancy following weight loss surgery were bowel obstructions, mostly internal hernias, which were rare but serious. The researchers identified 20 reports of complications requiring surgery, including instances in which three mothers and five neonates died. These complications can occur to anyone who has undergone bariatric surgery, Dr. Maggard noted.

Though some women suffered from nutritional deficits during their pregnancies, the problems appeared to be caused by their failure to take recommended supplements of multivitamins and iron, the review found.

One of the most urgent unresolved questions has to do with the effectiveness of oral contraceptives after weight loss surgery, Dr. Maggard said. So far, no randomized trials have assessed the effectiveness of birth control pills after bariatric procedures, including ones that affect the absorption of drugs and nutrients.

“Until we have some better answers about oral contraceptives, women should consider other methods, such as barrier methods, to prevent unwanted pregnancies,” Dr. Maggard said.

Another unanswered question has to do with how long women should wait before attempting pregnancy, Dr. Maggard added. “We advise them to defer pregnancy until after the time of rapid weight loss,” or about one year, she said.

The New York Times


Is health anxiety a significant problem for individuals with multiple sclerosis?

Although symptoms of anxiety and depression are often present in individuals with Multiple Sclerosis (MS), less is known about the role of health anxiety in this population.
J Behav Med. 2008 Nov 18. [Epub ahead of print]



Disease-Modifying Agents for Multiple Sclerosis : Recent Advances and Future Prospects.

Currently, six medications are approved for immunmodulatory and immunosuppressive treatment of the relapsing disease course and secondary-progressive MS.
Drugs. 2008;68(17):2445-2468. doi: 10.2165/0003495-200868170-00004.



Diagnostic workup of patients with acute transverse myelitis: spectrum of clinical presentation, neuroimaging and laboratory findings.

Clinical presentation of acute myelitis syndromes is variable, and neuroimaging and laboratory findings are not specific enough to establish the diagnosis with certainty.
Spinal Cord. 2008 Nov 18. [Epub ahead of print]



Mitomycin C-treated dendritic cells inactivate autoreactive T cells: Toward the development of a tolerogenic vaccine in autoimmune diseases.

Treatment of autoimmune diseases remains a challenge for immunological research. An ideal therapy should inhibit the immune reaction against the diseased organ and leave the rest of the immune response intact.
Proc Natl Acad Sci U S A. 2008 Nov 18. [Epub ahead of print]



Increased Osteopontin Expression in Dendritic Cells Amplifies IL-17 Production by CD4+ T Cells in Experimental Autoimmune Encephalomyelitis and in MS

Osteopontin (Opn) is a broadly expressed pleiotropic cytokine, and has been shown to play an important role in various autoimmune diseases, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE)
J Immunol. 2008 Dec 1;181(11):7480-7488.



Drak2 Regulates the Survival of Activated T Cells and Is Required for Organ-Specific Autoimmune Disease.

We present a model whereby T cell survival depends on a balance of TCR and costimulatory signals to explain how the absence of Drak2 affects autoimmune disease without generalized suppression of the immune system.
J Immunol. 2008 Dec 1;181(11):7593-7605.



Enhanced T Cell Apoptosis within Drak2-Deficient Mice Promotes Resistance to Autoimmunity.

Clonal expansion of T cells is vital to adaptive immunity, yet this process must be tightly controlled to prevent autoimmune disease.
J Immunol. 2008 Dec 1;181(11):7606-7616



Expression of TWEAK and Its Receptor Fn14 in the MS Brain: Implications for Inflammatory Tissue Injury.

The expression patterns of tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a pleiotropic cytokine with proinflammatory and cell death-inducing activities, and its receptor, fibroblast growth factor-inducible 14 (Fn14), were examined in postmortem brain tissue samples from patients with multiple sclerosis (MS) and controls.
J Neuropathol Exp Neurol. 2008 Nov 14. [Epub ahead of print]



SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination.

Thus, genetic factors and gender influence susceptibility to demyelinating disease in the cuprizone model, which may provide additional insights into the variability observed in human demyelinating diseases such as multiple sclerosis.
Brain Pathol. 2008 Oct 21. [Epub ahead of print]



Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early MS

Therapeutic targeting of the identified mechanisms of tissue injury might be crucial to prevent further lesion formation or secondary tissue damage.
Brain Pathol. 2008 Oct 31. [Epub ahead of print]



The role of specialist and general nurses working with people with MS

To describe the perceived role of nurses and other carers of people with multiple sclerosis from the perspective of different stakeholders (people with multiple sclerosis, non-specialist nurses, specialist nurses and other health care professionals).
J Clin Nurs. 2008 Nov 12. [Epub ahead of print]




Elan “Will Run Out of Money in 2 Years”

The clock is ticking for Elan Pharmaceuticals. Despite predicting it will record $1 billion in revenue in 2008, the company could run out of money in two years. The company is considering closing two U.S. facilities because its multiple sclerosis drug Tysabri is growing more slowly and doctors are worrying over whether it causes brain infections. Here’s the key nugget from Reuters:

In the nine months ended September 2008, Elan posted a net loss of $240.5 million. It is burning cash at a rate of more than $300 million a year, and it has $1.7 billion in debt that comes due over the next five years.

Another patient was reported with the PML brain infection in late October. The cases have hammered Elan’s stock and CEO Kelly Martin says he doesn’t think he can get a buyer for Elan’s drug technology business in the current market. The whole thing is pouring a lot of cold water on Elan-boosters who thought the company — and its shares — was ripe for takeover.




Review Article: MS and Reproductive Risks in Women

During the previous decades, women with Multiple Sclerosis (MS) were discouraged from having children, as pregnancy was deemed dangerous for pregnancy outcome and a contributing factor for exacerbation of MS. Current knowledge shows that women with MS are no more likely to have pregnancy or delivery complications compared to healthy women.
Sage Journals Online



Panel Confirms Gulf War Syndrome Is Real and Causes Are Definable

WASHINGTON, Nov. 17 -- The Gulf War illness was caused by pyridostigmine bromide pills taken by U.S. troops to neutralize the effects of nerve gas attacks and by exposure to neurotoxic insecticides, according to a VA advisory panel.

These two factors amounted to a definable scientifically valid illness with significant nervous system symptoms often still affecting veterans of the 1991 conflict in Kuwait and Iraq, said the Research Advisory Committee on Gulf War Veterans' Illnesses.

Exposures to neurotoxic compounds including insecticides -- which thousands of soldiers took as protection against nerve gas -- are the most likely causative candidates, added the report.

"Scientific evidence leaves no question that Gulf War illness is a real condition with real causes and serious consequences for affected veterans," the report said.

The committee was established and funded by congressional mandate. It delivered the report today to VA Secretary James Peake. The department is under no obligation to follow the report's recommendations, which run counter to the VA's long-standing position on Gulf War illness. In response to the report, the VA promised to "review and respond to the committee's recommendations in the near future."

The report estimated that about 175,000 to 210,000 of the approximately 700,000 deployed personnel "are affected by a complex of multiple symptoms, variously defined, over and above rates in contemporary military personnel who did not deploy to the Gulf War."

Symptoms typically include a combination of memory and concentration problems, persistent headache, unexplained fatigue, and widespread pain, and can also include chronic digestive difficulties, respiratory symptoms, and skin rashes.

"All available sources of evidence combine to support a consistent and compelling case that pesticide use during the Gulf War is causally associated with Gulf War illness," the report said.

In addition, as many as 250,000 personnel sent to the region took pills containing the carbamate pyridostigmine bromide to protect against potential nerve agent exposure.

Other key findings of the committee's report:

  • Exposures to low-level nerve agents such as sarin during destruction of Iraqi stockpiles, close proximity to oil-well fires, effects of multiple vaccinations, and combinations of exposures cannot be ruled out as causes of Gulf War illness.
  • Gulf War illness is associated with diverse biological alterations that most prominently affect the brain and nervous system.
  • Gulf War illness differs significantly from multi-symptom conditions such as fibromyalgia in the general population, although there are similarities as well.
  • Gulf War veterans have significantly higher rates of amyotrophic lateral sclerosis than other veterans.
  • Gulf War veterans potentially exposed to nerve agents have died from brain cancer at elevated rates.

The committee recommended that Congress budget at least $60 million annually for new research on Gulf War illness.

It said research into treatments was the most pressing need. The report also called for studies into objective biological markers of the syndrome as well as additional epidemiological research.

MedPage Today


Decreased T-cell reactivity to Epstein-Barr virus-infected lymphoblastoid cell lines in MS

To investigate T-cell and antibody immunity to Epstein–Barr virus (EBV) in multiple sclerosis (MS).
JNNP Online - Journal of Neurology Neurosurgery & Psychiatry



Sheffield Hallam University (UK) Explores Exercise Intervention For MS Sufferers

Sheffield Hallam University has been awarded a new £200,000 research grant to investigate the effects of exercise intervention on sufferers of multiple sclerosis (MS). The MS Society has awarded the grant to the University's Centre for Sport and Exercise Science, which will study the effects of exercise therapy on physical activity and health outcomes in people living with MS. Led by Dr John Saxton, a Reader in Clinical Exercise Physiology, the grant becomes the third received from the Society by Sheffield Hallam University.

"Living with multiple sclerosis is a difficult experience both physically and mentally," said Dr Saxton. "This has created a need for clinicians and researchers to address issues that are related to the long-term health-related quality of life for people with the condition. Our study will tackle some important questions, the answers to which we hope will not only help people with MS but also the organisations which must budget for their treatment."

The project will measure physical activity, aerobic function, physical function and health related quality of life before and after a 12-week exercise plan. Participants will be followed for three months after the interventions to provide an indication of whether any benefits have been sustained.

"The award of this grant is a real endorsement by the MS Society," says Dr Saxton. "Together we hope to provide valuable and vital insights to help alleviate the difficulties for people living with MS."

"For many people with MS, remaining active through exercise is hugely beneficial and it is important to understand what exercise is most helpful and what health benefits it brings."

The study will be partnered with Sheffield Teaching Hospitals NHS Trust and the University of Birmingham. About the study

The effects of a pragmatic exercise therapy intervention on physical activity and important health outcomes influencing maintenance in people with multiple sclerosis

120 people with MS will be recruited to the study, who will then be randomized to either receive the 12 week exercise programme or usual care.

A range of outcome measures will be assessed in order to evaluate the effectiveness of the exercise programme. These include physical activity levels of the participants, neurological assessments including EDSS, and a range of quality of life measures including measures of fatigue.
Medical News Today


Environment Causes Increase In Multiple Sclerosis Among Women Only

Gender has become a dominant factor in Multiple Sclerosis (MS) during the last decades. Already with a ratio of 3.2 to 1 MS is gradually changing into a disease predominantly among women. Since genetic factors can be ruled out as a cause of this gender related increase, scientific attention is on environmental factors that may increase MS risk in women exclusively. Most likely environmental factors include smoking, viral infections, Vitamin D deficiency, hygiene changes and dietary factors.

Almost 400 MS scientists and clinicians from around the world gathered this week during a medical scientific conference on 'Multiple Sclerosis and Gender', organized by the independent European Charcot Foundation, to share and discuss their scientific views on the backgrounds of this major shift in gender ratio.

One of the main focal points in the gender related approach is the effect of pregnancy on disease progression in MS. The disease practically disappears during the last trimester of pregnancy. Why is that and can we use our vast knowledge of natural female sex hormones, such as estriol, progesterone and prolactin, to develop new ways of treating women with MS? Several phase III clinical trials are already underway that will provide answers to this question by the end of 2009.
Medical News Today



Bone health in ambulatory individuals with MS: Impact of physical activity, glucocorticoid use, and body composition.

This study examined the relationships among physical activity, glucocorticoid use, body composition, and bone health in ambulatory women with multiple sclerosis (MS).
J Rehabil Res Dev. 2008;45(6):851-62.


Mitochondrial Mutation in Iranian Patients with Multiple Sclerosis, Correlation Between Haplogroups H, A and Clinical Manifestations.

As multiple sclerosis (MS) has long been known to be associated with Leber, hereditary optic neuropathy (LHON), a disease caused by mitochondrial (mtDNA) mutations, in this study we assessed possible involvement of mtDNA point mutation in MS patients.
Cell Mol Neurobiol. 2008 Nov 14. [Epub ahead of print]


Preserved decision making ability in early multiple sclerosis.

The purpose of this study was to assess decision making in patients with multiple sclerosis (MS) at the earliest clinically detectable time point of the disease.
J Neurol. 2008 Nov 13. [Epub ahead of print]


Recognizing nonadherence in patients with MS and maintaining treatment adherence in the long term.

Patients with multiple sclerosis (MS) face many challenges. One significant challenge is long-term adherence to disease-modifying therapy (DMT).
Medscape J Med. 2008;10(9):225. Epub 2008 Sep 30.


Why Patients Go Online: Multiple Sclerosis, the Internet, and Physician-Patient Communication.

Most MS patients are informed by online information, but are unlikely to discuss that research with physicians for reasons that may have implications for patient adherence.
Neurologist. 2008 Nov;14(6):374-381.


Central vertigo and dizziness: epidemiology, differential diagnosis, and common causes.

This article provides an overview of the epidemiology of dizziness, differentiating between central and peripheral vertigo, and central causes of dizziness.
Neurologist. 2008 Nov;14(6):355-64.


Differential induction of experimental autoimmune encephalomyelitis by myelin basic protein molecular mimics in mice humanized for HLA-DR2 and an MBP

Multiple sclerosis (MS) is a chronic autoimmune neurological disease characterized by infiltration of peripheral inflammatory cells to the central nervous system (CNS) and demyelination of CNS white matter.
J Autoimmun. 2008 Nov 11. [Epub ahead of print]


Segmentation of brain magnetic resonance images for measurement of gray matter atrophy in MS patients.

Measurement of GM volumes is a particularly useful method to estimate the total extent of GM tissue damage because it can be done with conventional magnetic resonance images (MRI).
Neuroimage. 2008 Oct 22. [Epub ahead of print]


Cognitive impairment in multiple sclerosis.

The increased use of neuroimaging techniques in patients with MS has advanced our understanding of structural and functional changes in the brain that are characteristic of this disease, although much remains to be learned.
Lancet Neurol. 2008 Dec;7(12):1139-1151.


Targeting PPAR as a therapy to treat multiple sclerosis.

PPAR agonists regulate MS-like disease in animal models by blocking inflammatory signaling pathways, suggesting their use in treatment of MS. Current human trials are likely to confirm the safety and efficacy of PPAR agonists for MS treatment.
Expert Opin Ther Targets. 2008 Dec;12(12):1565-1575.


Multiple sclerosis and allied white matter diseases.

Future improvements, including the development of new sequences and post-processing methods as well as the use of high-field MRI, despite being a major technical challenge, hold new and exciting promise.
Neurol Sci. 2008 Oct;29 Suppl 3:319-22


A Longer, Better Life

Author Sara Davidson talks to two medical scientists about how the body ages and the research on trying to extend our healthy life span.
The New York Times - Magazine - Video interview



Pharmacogenomics of MS: in search for a personalized therapy.

In this review we examine the pharmacogenetic studies that have evaluated the clinical response to interferon-beta, and to a lesser extent, glatiramer acetate and natalizumab. Finally, we discuss how systems biology can be used to integrate biological and clinical data in order to develop personalized medicine for MS.
Expert Opin Pharmacother. 2008 Dec;9(17):3053-3067.



Basic and escalating immunomodulatory treatments in MS: Current therapeutic recommendations.

This review updates and extends earlier Consensus Reports related to current basic and escalating immunomodulatory treatments in multiple sclerosis (MS).
J Neurol. 2008 Oct;255(10):1449-63. Epub 2008 Oct 29



Systems biology approaches for the study of multiple sclerosis.

MS is thought to result from a complex interaction between genetic and environmental factors.
J Cell Mol Med. 2008 Aug;12(4):1087-93. Epub 2008 May 26




Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis

This study investigated sample sizes required to demonstrate reduction of brain atrophy using three outcome measures in a parallel group, placebo-controlled trial for secondary progressive MS (SPMS).



Smoking Status over Two Years in Patients with Multiple Sclerosis.

Smoking increases the risk of multiple sclerosis (MS) and possibly disease progression. The reliability of self-reported smoking status is unknown in MS.
Neuroepidemiology. 2008 Nov 12;32(1):72-79. [Epub ahead of print]



Favorable effect of immunomodulator therapy on bone mineral density in multiple sclerosis.

Osteoporosis is a complication of multiple sclerosis (MS), especially if corticosteroid therapy is given. Little is known about the effect on bone of immunomodulatory therapy (IMT) for MS.
Ir J Med Sci. 2008 Nov 12. [Epub ahead of print]



Lymphatic drainage of the brain and the pathophysiology of neurological disease.

There are no conventional lymphatics in the brain but physiological studies have revealed a substantial and immunologically significant lymphatic drainage from brain to cervical lymph nodes.
Acta Neuropathol. 2008 Nov 11. [Epub ahead of print]



Persistence of immunopathological and radiological traits in multiple sclerosis.

Our observations support the concept of intraindividual homogeneity of a given immunopathological MS subtype.
Arch Neurol. 2008 Nov;65(11):1527-32.



Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive MS

Gray matter magnetization transfer ratio meets many of the criteria for a surrogate marker of progression in early PPMS.
Arch Neurol. 2008 Nov;65(11):1454-9.



Predicting clinical progression in multiple sclerosis with the magnetic resonance disease severity scale.

Combining brain MRI lesion and atrophy measures can predict MS clinical progression and provides the basis for developing an MRI-based continuous scale as a marker of MS disease severity.
Arch Neurol. 2008 Nov;65(11):1449-53.



Interferon Beta-induced restoration of regulatory T-cell function in MS is prompted by an increase in newly generated naive regulatory T cells

The increase in T(reg)-cell inhibitory capacity mediated by interferon beta treatment can be explained by its effect on the homeostatic balance within the T(reg) cell compartment.
Arch Neurol. 2008 Nov;65(11):1434-9.



Heterogeneity in Response to Interferon Beta in Patients With MS: A 3-Year Monthly Imaging Study.

Multiple MRI evaluations disclose that approximately only half of the patients treated with interferon beta achieve and maintain a full response to the drug over time, although an additional small number of individuals may still restore an optimal response to the drug after an initial failure.
Arch Neurol. 2008 Nov 10. [Epub ahead of print]



A review of the current use of rituximab in autoimmune diseases.

Rituximab is a human/murine chimeric monoclonal antibody primarily used for treating non-Hodgkin's B-cell lymphoma. Recently it is also used in the treatment of several autoimmune diseases. A literature review was conducted to determine the efficacy of rituximab in the treatment of some of these autoimmune diseases.
Int Immunopharmacol. 2008 Nov 7. [Epub ahead of print]



Protective autoimmunity in the nervous system.

The beneficent aspects of the immune response in the nervous system are beginning to be appreciated and their potential as pharmacologic targets in neurologic disease is being explored.
Pharmacol Ther. 2008 Nov 1. [Epub ahead of print]



Effects of dietary intervention on MRI activity, de- and remyelination in the cuprizone model for demyelination.

The aim of this study was to analyse if diets with a different composition of polyunsaturated fatty acids (PUFAs) could influence demyelination and remyelination in cuprizone fed mice, a widely used animal model for de- and remyelination.
Exp Neurol. 2008 Oct 22. [Epub ahead of print]



Prospective memory and the efficacy of a memory strategy in multiple sclerosis.

Prospective memory (PM), which is the ability to remember to carry out actions that are planned for the future, plays an important role in professional and social life as well as in activities of daily living. This study examined PM performance among adults with multiple sclerosis (MS) and evaluated the efficacy of a mnemonic strategy, implementation intentions.
Neuropsychology. 2008 Nov;22(6):746-54.



Top 7 Health Concerns for Women and What to Do About Them-Cleveland Clinic


It is one of 4,613 stories on our MySpace Blog!

Our 3,300 MySpace Friends have made 29,896 Comments & 42,234 Kudos on the 4,613 stories!


Cleveland Clinic Preventive Medicine Expert Offers Tips

When we're young, most of us don't worry much about our health. But starting in our late 30s, some health concerns start nagging at us. Or we notice our friends grappling with health problems.

Major health concerns vary by age, says Cleveland Clinic preventive medicine expert Raul Seballos, MD. "For example, women begin to grow concerned about menopause in their 50s and start to worry about osteoporosis in their 60s," he notes. Here are the major health concerns for women, along with tips for prevention:

1 Cancer

Breast cancer. Lower your risks by not smoking, exercising regularly, limiting alcohol use and controlling your weight. In your 20s and 30s, have clinical breast exams every three years, and at age 40, start getting yearly mammograms. You may need earlier, more frequent screening if you have breast cancer in the family or other risk factors.

Cervical cancer. Get your annual Pap smear to screen for cervical cancer; yearly Pap smears reduce both cervical cancer incidence and mortality.

Colon cancer. Start screening at age 50 with annual high-sensitivity fecal occult blood testing, and flexible sigmoidoscopy every five years or colonoscopy every 10 years. All three methods are effective in reducing colorectal cancer mortality.

2 Cardiovascular disease/high blood pressure/high cholesterol

If cardiovascular disease runs in your family, or if your blood pressure or cholesterol levels are high, ask your doctor about taking medications to control blood pressure and cholesterol. Your doctor can also advise you on whether you'll benefit from taking a daily aspirin.

3 Osteoporosis

To preserve bone mass, avoid cigarettes, limit your alcohol intake, get adequate calcium and Vitamin D, and do weight-bearing exercises such as walking. Risks of bone fragility are greatest after menopause, so supplement your diet with 1,200 mg of calcium plus 800 to 1,000 IU of Vitamin D3 starting at age 50. Begin bone-mineral density screenings at age 65, or earlier if you have one or more risk factors (at age 50 if you've suffered a bone fracture.) Screening every two or three years will detect any bone-thinning, and you can take bone-building medications on a weekly, monthly or annual (intravenous) basis if needed.

4 Menopause treatment options

If lack of sleep, continuous hot flashes or severe mood swings are disrupting your life, consider hormone replacement therapy. Take the lowest dose of hormones you need to relieve symptoms, for the shortest period of time. Avoid 'bioidentical' hormones from compounding pharmacies, the U.S. Food and Drug Administration warns; they aren't effective. Your physician will guide you to the right hormone combination and best mode of administration.

5 Weight management as you get older

Eat smaller portions and healthier foods, and exercise more as your metabolism slows down with age. This will help prevent type 2 diabetes, arthritis and other weight-related problems.

6 Diabetes

Nearly 60 million Americans have pre-diabetes (elevated blood sugar), the precursor to type 2 diabetes. Type 2 diabetes can lead to heart disease, stroke, kidney failure, blindness and loss of limb. Studies now prove that a healthier diet and increased activity can restore normal blood sugar levels and prevent diabetes. It's critical to control weight, cholesterol and blood pressure, and to quit smoking as well.

7 Stroke

Take one baby aspirin daily starting at age 65; it may help to prevent stroke. Meanwhile, call 9-1-1 if you see anyone develop weakness or numbness of the face, arm or leg(s); confusion; speech or comprehension problems; vision loss; dizziness; or difficulty with walking, balance or coordination. These are early warning signs of stroke, and immediate treatment can be lifesaving.



Painkiller Risk Found for Heart Patients

Heart attack and heart failure patients have a higher risk of a second heart attack or death if they take painkillers, including the generic drug ibuprofen and Celebrex, made by Pfizer, a Danish study has found.

Patients who had suffered a heart attack and were taking Vioxx, a painkiller that has been withdrawn from the market, had 2.7 times the risk of having another heart attack or dying compared with patients not taking painkillers, according to research presented Tuesday at the American Heart Association meeting in New Orleans. Patients taking Celebrex had double the risk; patients taking the generic diclofenac had 1.9 times the risk, and those taking ibuprofen had 1.3 times the risk, the study found.

Based on the findings, doctors should avoid prescribing nonsteroidal anti-inflammatory drugs for these patients, or give them at low doses, a researcher said.

Also Tuesday, researchers said that the risk of heart attacks and strokes for heart-stent patients taking the anti-clotting drug Plavix increased if they also took anti-ulcer medicines like Nexium.

Doctors implant about two million stents a year and often prescribe blood thinners like Plavix, made by Bristol-Myers Squibb and Sanofi-Aventis, to avoid clots. But the drugs raise the risk of stomach bleeding, so they also prescribe Nexium, made by AstraZeneca, or a rival drug in a group known as proton pump inhibitors. About a third of these patients suffered complications within a year, the study said.

The New York Times



Kennedy Works to Draft Obama-Based Healthcare Overhaul Bill

WASHINGTON, Nov. 6 -- Key Congressional figures led by Sen. Edward Kennedy (D-Mass.) are wasting no time drafting a major healthcare bill modeled after President-elect Barack Obama's sweeping overhaul plan.

"With the Obama victory, the question is no longer whether we'll pursue comprehensive healthcare reform, but when and in what form," said Michael Myers, staff director for the Senate Health, Education, Labor, and Pensions (HELP) committee, which Kennedy chairs.

Kennedy has spent the past weeks preparing for an Obama victory by meeting with the Senate Finance Committee and key healthcare stakeholders to nail down specifics about how to restructure the healthcare system, said Myers.

While the specifics of the healthcare legislation meetings are under wraps, Myers said to expect a single bill largely mirroring Obama's healthcare plan as outlines in broad brushes during the campaign.

Obama's plan would require that all children have insurance and would mandate that employers offer coverage to their employees. It would also create a national insurance plan as well as an insurance exchange program, which would allow people to purchase insurance on a national market from a variety of providers. Their coverage must at least equal that provided to federal employees.


Relevance of the skewness index in DTI exploration of multiple sclerosis.

To this day, no parameter can really monitor the progression of multiple sclerosis (MS). In this study, an index the skewness (S) derived from parameters calculated in diffusion tensor imaging (DTI) has been tested on MS patients for its ability to monitor the disease course.

PubMed -

MAGMA. 2008 Nov 8. [Epub ahead of print]


Neurodegeneration and neuroprotective agents in multiple sclerosis.

New therapeutic strategies targeting the neurodegenerative process in MS provide hope to the MS community. A number of phase II or III clinical trials that are designed to target such specific pathogenetic mechanisms include sodium channel blockers, matrix metalloproteinases (MMP) inhibitors, c-AMP selective phosphodiesterase inhibitors, NMDA receptor antagonists, amongst others.



Gender hormones: role in the pathogenesis of central nervous system disease and demyelination.

Gender hormones are associated with the evolution of Multiple Sclerosis (MS) like changes in experimental models of MS.



Challenges in Multiple Sclerosis: Emerging Data in an Evolving Therapeutic Landscape

Release Date: October 31, 2008; Valid for credit through October 31, 2009

Credits Available
Physicians - maximum of 1.0 AMA PRA Category 1 Credit(s)™ for physicians

To participate in this internet activity: (1) review the target audience, learning objectives, and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation; (4) view/print certificate View details.

Contents of This CME Activity
Challenges in Multiple Sclerosis: Emerging Data in an Evolving Therapeutic LandscapeOmar Khan, MD; Daniel Kantor, MD; Adil Javed, MD
Go to CME Test Questions

Legal Disclaimer
The material presented here does not necessarily reflect the views of Medscape or companies that support educational programming on These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.



EMD Serono plans expansion for 2009

One of the nation’s leading biopharmaceutical companies will break ground early next year for an approximately $75 million expansion to its current Billerica research facility.

The company, which focuses its studies on therapeutic areas of neurology, fertility, endocrinology, oncology and other autoimmune inflammatory diseases, employs 1,000 workers nationwide, according to Heather Hatfield, director of U.S. Communications for EMD Serono. At present 650 of the 1,000 employees are spread across the company’s U.S. headquarters in Rockland and its Billerica facility.

“We’ve had a strong presence in Massachusetts for more than 25 years,” said Hatfield. “Our Billerica facility has been in existence for several years, with a focus on research in oncology and fertility and we’ll most likely expand into neurology in the near future as well as early stage manufacturing.”

Neurology is an important part of the company, with a large focus around its flagship product, Rebif, used to treat relapsing multiple sclerosis (MS). The next step for EMD Serono in their efforts to help patients living with neurodegenerative diseases is bringing the first oral therapy for MS, cladribine, to the market.

Hatfield said the company is very excited about the potential the drug, which is in late-stage trials, will bring to patients.



Biogen Idec raises price of MS drug again

Biogen Idec Inc. has raised the wholesale price of one of its flagship drugs, Avonex, for the fifth time in two years, according to a note by JP Morgan analyst Geoffrey Meacham. The Cambridge biotech company raised the price of the multiple sclerosis drug by 8.9 percent on Nov. 8.

Meacham said that nearly matches a recent 9.5 percent increase for rival drug, Rebif, made by Rockland-based EMD Serono Inc. Avonex now costs about $27,000 for a year's supply, about $1,000 less than Rebif.

The Boston Globe -

Labels: ,


Half of Multiple Sclerosis Patients Fail Interferon Therapy

BETHESDA, Md., Nov. 10 -- Only eight of 15 relapsing-remitting multiple sclerosis patients treated with interferon achieved and maintained a full response over three years, a small retrospective imaging study found.

Two of the seven non-responders went on to achieve an optimal response after initial failure, Francesca Bagnato, M.D., Ph.D., of the National Institute of Neurological Disorders and Stroke, and colleagues reported online in Archives of Neurology.

This delayed response, the researchers said, suggests that frequent MRI monitoring is warranted during the first year of therapy.

MRI visualizes inflammatory plaques, namely contrast-enhancing lesions (CELs), in patients with multiple sclerosis. These lesions precede clinical relapses, which in turn are presumed to lead to disease progression, the researchers said.

Although clinical studies have shown that interferon beta can reduce these lesions, little is known about the heterogeneity of the MRI response profiles between patients or within an individual patient over time, the researchers wrote.

To get that sort of data, this open-label study at the National Institutes of Health, analyzed and described in detail the MRI responses to interferon beta in a cohort of 15 patients with relapsing-remitting MS.

Eight patients (53.3%) were MRI responders, showing a reduction of 60% or more in activity of the total number of lesions.

However, three of the MRI responders had clinical relapses during the first six months of therapy, and two of these had a sustained progression in the Expanded Disability Status Scale (EDSS).

Of the seven non-responders (46.7%), three (20.0% of the original study group) had only an initial optimal reduction in the total number of lesions, but no further change. Two (13.3%) never reached an optimal response.

However, two of the seven non-responders (13.3% of the total group) did reach and maintain a response of 60% or more after the first six months on therapy.

All seven of the non-responders experienced at least one clinical exacerbation during the treatment phase.

Neither MRI nor clinical parameters at the beginning of the study predicted which of the patients would be not respond to therapy. However, because the number of patients was small, a definitive conclusion is not possible, the researchers said.

One could argue, they said, that changes with treatment might be more easily identified in patients with a higher total number of lesions. However, on close inspection of the data, overall the total number of lesions among different responder types was heterogeneous.

The novel aspect of this study is the unique number of monthly MRIs done for each patient, potentially disclosing information masked by approaches using less frequent measurements, the investigators said.

MedPage Today



Warning over untested web 'cures'

Leading medical experts are warning patients against using untested remedies advertised on the internet which, they say, sell "false hope".

The group, backed by charity Sense About Science, says vulnerable people are being increasingly exploited by the online promotion of such treatments.

A new guide has been published to help patients recognize bogus treatments.

Sense About Science says there are now hundreds of websites offering hope to people who are desperate for a cure.

Some offer stem cell treatments for brain disorders for tens of thousands of pounds. Others sell cures for multiple sclerosis and cancers.

Dr Kieran Breen, director of research at the Parkinson's Disease Society, said: "It can be tempting to believe personal stories of miracle cures, but only by using tried and tested methods can we move forward and provide people with Parkinson's with the best available advice and treatments."

Lib Dem MP Phil Willis, chairman of the Innovation, Universities, Science and Skills Select Committee, said the "cruelest deception" for a patient with chronic illness was the promise of a cure based on "empty hope not evidence".

Ian Douglas, who has multiple sclerosis, agreed, saying patients with incurable conditions found hope in short supply and looked for anything that might help.

A new guide, called I've got nothing to lose by trying it, has been published by Sense About Science with the Multiple Sclerosis Society, Motor Neurone Disease Association, Alzheimer's Society and Parkinson's Disease Society.

It aims to help patients tell the difference between beneficial remedies and bogus treatments.

Click for link to video titled Let Down By Untested Remedies with an arthritis sufferer Daniella Muallem's experience of using alternative remedies:

Let Down By Untested Remedies - video




The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with MS.

Contrast enhancing lesions (CELs) in MRI represent inflammatory events in multiple sclerosis (MS). IFN-beta-1b decreases the formation of CELs. However, the ability of IFN-beta-1b to reduce the size of CELs arising during therapy has not been extensively investigated.



Neuromyelitis optica and asian phenotype of multiple sclerosis.

This review discusses possible mechanisms for OSMS and anti-AQP4 autoimmune syndrome of the CNS.



Residence Near Power Lines and Mortality From Neurodegenerative Diseases: Longitudinal Study of the Swiss Population.

The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000-2005.





It is one of 4,613 stories on our MySpace Blog! Our 3,300 MySpace Friends have made 29,896 Comments & 42,234 Kudos on the 4,613 stories!


"Riken researchers make brain tissues from stem cells"

Friday 07th November, 07:35 AM JST

KOBE — Japanese researchers said Thursday they had created functioning human brain tissues from stem cells, a world first that has raised new hopes for the treatment of disease. Stem cells taken from human embryos have been used to form tissues of the cerebral cortex, the supreme control tower of the brain, according to researchers at the government-backed research institute Riken.

The research was led by Yoshiki Sasai at Riken Center for Development Biology in Kobe.

The tissues self-organized into four distinct zones very similar to the structure seen in human fetuses, and conducted neuro-activity such as transmitting electrical signals, the institute said.

Research on stem cells is seen as having the potential to save lives by helping to find cures for diseases such as cancer and diabetes or to replace damaged cells, tissues and organs.

The team's previous studies showed stem cells differentiated into distinct cells but until now they had never organized into functioning tissues.

"In regenerative therapy, only a limited number of diseases can be cured with simple cell transplants. Transplanting tissues could raise hopes for greater functional recovery," the institute said in a statement.

"Cultivated tissues are still insufficient and too small to be used to treat stroke patients. But study of in-vitro cultivation of more mature cortex tissues, such as those with six zones like in the adult human brain, will be stepped up," it said.

The tissues could also serve as "a mini organ" for use in studying the cause of the Alzheimer's disease and developing vaccines, it said.

Embryonic stem cells are harvested by destroying a viable embryo, a process that some people find unacceptable.

Riken said cortex tissues were also obtained from "induced pluripotent stem cells," which are similar to embryonic stem cells but artificially induced, typically from adult cells such as skin cells. The cultivated tissues look like miniature mushrooms two millimeters in diameter.

The team also succeeded in making cortex tissues from the embryonic stem cells of mice. Using mouse tissues, scientists confirmed they had formed a network of neurons that properly respond to stimulus.

The tissues can also be selectively induced to different cortex types controlling memories, visual sensation and other tasks.

The findings of the study were published in the Nov 6 online journal Cell Stem Cell in the United States.



Balance-based torso-weighting in a patient with ataxia and multiple sclerosis: a case report.

This case report describes the effect of torso-weighting to counteract directional balance loss in a woman with relapsing/remitting multiple sclerosis.



Nuanced roles of cytokines in three major human brain disorders.

The three most prevalent human disorders of the CNS in which immunity and inflammation are likely to have vital roles (excluding infection of the CNS) are fever, multiple sclerosis (MS), and Alzheimer disease (AD). As reviewed here, cytokines are critical in the induction of fever, the pathogenesis of MS, and the pathobiology of AD.

PubMed - Journal of Clincial Investigation


Clinical and diagnostic aspects of MS and acute monophasic encephalomyelitis in pediatric patients: a single centre prospective study

Our findings depict a pattern of demographic, clinical, neuroimaging, and laboratory findings that can help to distinguish, at clinical onset, children suffering from ADEM from those who will develop MS. Childhood-onset MS seems not to differ from adult-onset MS from both clinical and paraclinical features.

Sage Journals Online


Natalizumab: increased vigilance is required in treating patients with multiple sclerosis

The recent repor ting of two new cases of progressive multifocal leukoencephalopathy (PML) in
patients with multiple sclerosis (MS) receiving natalizumab highlights the risks associated with this agent in patients who do not respond to conventional immunomodulatory therapy.

Sage Publications

Labels: ,


Natalizumab: benefit outweighs risk in selected patients with multiple sclerosis

Full PDF article available at:

Sage Publications


The results of two multicenter, open-label studies assessing efficacy, tolerability and safety of protiramer

a high molecular weight synthetic copolymeric mixture, in patients with relapsing–remitting multiple sclerosis

Two pilot studies were conducted to evaluate safety, tolerability, and efficacy of two doses of Protiramer (TV-5010) in patients with relapsing–remitting multiple sclerosis.

Multiple Sclerosis 2008, doi:10.1177/1352458508098269
Sage Journals OnLine


Brain atrophy evolution and lesion load accrual in MS: a 2-year follow-up study

In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

Multiple Sclerosis 2008, doi:10.1177/1352458508098270
Sage Journals Online


Clean intermittent self-catheterization in persons with MS: the influence of cognitive dysfunction

The aim of this study was to investigate the ability of PwMS to learn clean intermittent self-catheterization (CISC).

Multiple Sclerosis 2008, doi:10.1177/1352458508098599
Sage Journals Online


Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways

Our results suggest that the symptom of fatigue is associated with a disruption of brain networks involved in cognitive/attentional processes.

Multiple Sclerosis 2008, doi:10.1177/1352458508098373
Sage Journals Online


Review: Recombinant human erythropoietin: novel strategies for neuroprotective/neuroregenerative treatment of MS

Treatment of multiple sclerosis (MS) is still unsatisfactory and essentially non-existing for the progressive course of the disease. Recombinant human erythropoietin (EPO) may be a promising neuroprotective/neuroregenerative treatment of MS.

Therapeutic Advances in Neurological Disorders, Vol. 1, No. 3, 193-206 (2008)
Sage Journals OnLine


Review: Escalating immunotherapy of MS

This article will review potential candidates for intensified immunosuppression and call for innovative study designs to better evaluate escalating immunotherapy in MS.

Therapeutic Advances in Neurological Disorders, Vol. 1, No. 3, 181-192 (2008)
Sage Journals OnLine


Cannabislike Drugs May Hold Key to Treating Pain While Bypassing the Brain

Although the therapeutic properties of marijuana, or cannabis, have been of interest for years, the substance's unwanted effects and its illegal status as a street drug have made its medical use controversial.

CB1, which is expressed in both the brain and the peripheral nervous system, is well-known for being involved in pain relief. Now scientists have found that CB1 expression is lost in most colorectal cancers.

Scarcity of CB1 also is associated with Huntington disease, Alzheimer disease, and multiple sclerosis, but the receptor's role in these diseases is unclear.

JAMA - Journal of the American Medical Association
 Vol. 300 No. 17, November 5, 2008 Vol. 300 Vol. 300 No. 17, November 5, 2008 No. 17, November 5, 2008


Immunologic and clinical status 14 months after cessation of natalizumab therapy

This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.




Identification of soluble TREM-2 in the cerebrospinal fluid and its association with MS and CNS inflammation

The elevated levels of sTREM-2 in CSF of multiple sclerosis patients may inhibit the anti-inflammatory function of the membrane-bound receptor suggesting sTREM-2 to be a possible target for future therapies.

Oxford Journals - BRAIN A Journal of Neurology


Up-regulation of slow K+ channels in peripheral motor axons: a transcriptional channelopathy in MS

This study thus provides evidence for plasticity in motoneuronal properties at a molecular level, the first such evidence for intact human subjects.

Oxford Journals - BRAIN a Journal of Neurology


A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in MS

Our results suggest that in active-multiple sclerosis, there is a shift in the lipid composition of NAWM and NAGM to a higher phospholipid and lower sphingolipid content.

Oxford Journals - BRAIN a Journal of Neurology




It is one of 4,613 stories on our MySpace Blog! Our 3,300 MySpace Friends have made 29,896 Comments & 42,234 Kudos on the 4,613 stories!


Tysabri: The Big Multiple Sclerosis Drug That Emerged From "The Hutch

The most effective drug on the market today for patients with multiple sclerosis has roots in a dingy old lab in the 1980s on Seattle's First Hill. It was there that a pair of young scientists at the Fred Hutchinson Cancer Research Center, Bill Carter and Elizabeth Wayner, made key discoveries that paved the way for natalizumab (Tysabri).

The treatment has become the fastest-growing product for Cambridge, MA-based Biogen Idec (NASDAQ: BIIB) and its Irish partner Elan (NYSE: ELN), and it's projected to generate $1.6 billion in sales in 2011. Most people know of its link to a rare, often fatal brain infection called PML, and its dramatic recovery. But few people know where the drug comes from.

So I stopped by Carter's new lab at the South Lake Union campus of "The Hutch" to hear the story.

Carter, 62, didn't seem the least bit self-important about this discovery when I stopped by his office last week. He wore a brown T-shirt and brown sandals. Manila file folders with scientific papers were stacked high on the shelves in his office. He didn't care much to discuss the financial and legal aspects of this story, but when the subject turned to the science, Carter's eyes lit up with boyish enthusiasm.

He got his doctorate at the University of California-Davis in 1974, where he studied how cells bind to each other, or cell adhesion. After a yearlong fellowship in Israel, he joined the Hutch as a postdoc, shortly after it was founded in 1975. Specifically, he wanted to learn more about the adhesion properties of epithelial cells, those that form linings or boundaries between tissues like skin or other organs. He was interested in these cells because they are involved in most adult cancers.

Those cells remain in a non-active state most of the time, but can become highly activated in the case of an injury, Carter says. For example, when a person falls off a bicycle and scrapes a knee, these epithelial cells leap into action. The cells work to close the wound, secrete proteins that trigger an immune system reaction that mop up all the foreign invaders like bacteria. Other cells, platelets, pour in to the area to form clots.

"Everything is moving in that area to cope with disaster," Carter says.

This whole process requires big-time changes in cell adhesion properties. By the early to late 1980s, when Carter was pursuing this work on the third floor of Eklind Hall (an old building on Seattle's First Hill that Xconomy Seattle proudly calls home today), scientists knew very little about this cell adhesion process or the proteins on the surface of cells. "None of the components were known," Carter says.

One way to identify these components was to develop targeted antibodies that would bind with and block receptors ..s. Carter and his colleagues found GP-140, a new type of protein. This was important because it led to the development of methods to identify more adhesion receptors on the surface of cells, and what they interact with. It was the spark that set Carter and his lab partner Elizabeth Wayner off to the races for the next five years. "We said let's hunt for different adhesion receptors" ..s, which could serve as new antibody drug targets.

Wayner was one of the scientists who came into Carter's lab as an immunology postdoc. The biggest step ahead for these two was when they made antibodies that identified a new cell surface receptor called alpha4 beta1. Wayner and Carter, in a paper in 1989 in the Journal of Cell Biology, identified one antibody in particular called P4C2 that they said "completely inhibited" binding to this target. It's now the target—today called an integrin—which is hit by the natalizumab (Tysabri) antibody.

Carter and Wayner's work later veered in different directions.

He looked more at epithelial biology and at triggers that control migration of epithelial cells, which play a role in 80 percent of cancers, Carter says. Wayner focused more on integrins, and blocking killer T cells from binding with them.

This integrin work appears to have more broad application than just with multiple sclerosis. The Biogen and Elan drug is FDA-approved for Crohn's disease, an inflammatory condition of the large intestine, and is in clinical trials for multiple myeloma, a deadly cancer of the bone marrow.

The intellectual property never turned into the basis for a standalone biotech company in Seattle, although it was licensed for a time to a small startup called Oncogen. That company ultimately went out of business and handed the integrin-based intellectual property back to the Hutch, Carter says. Eventually, the IP got into the hands of Elan, which formed a partnership to co-develop and co-market the drug with Biogen in August 2000.

This treatment was approved by the FDA in November 2004 as the first of its kind to stop inflammatory white blood cells from migrating across the blood brain barrier and attacking the fatty coating around nerve cells in the brain. It showed it could reduce the risk of MS flare-ups by two-thirds compared to a placebo—about twice as effective as the standard immune-suppressing interferon beta drugs.

But three months later, Biogen and Elan yanked it off the market after two patients were found to have PML. After protests from patients, the drug was re-introduced in July 2006; the FDA determined the benefit outweighed the risk. The drug generated $343 million in sales last year, and is now being taken by about 35,000 patients worldwide. It is projected to generate $1.6 billion in sales in 2011, according to Christopher Raymond, an analyst with Robert W. Baird in Chicago.

This all means a lot today to "The Hutch." The patent, licensed to Elan, covers methods of using an antibody drug against the alpha4 integrin, a protein on the surface of white blood cells that the drug hits. The patent was issued in March 1998 and lasts until 2015, says Ulrich Mueller, the center's vice president of industry relations and technology transfer. The Hutch isn't saying what percentage royalty it gets on sales because of a confidentiality agreement, although it's common in the industry for such licenses to be worth 1 percent of sales. (If it's truly generating a 1 percent royalty on a $1 billion-a-year drug, that means the Hutch could collect $10 million annually in royalties. Assuming no more PML cases damage the drug, it could be a serious boost for the organization, which generated $3.4 million in total licensing income in fiscal 2006, according to a survey by the Association of University Technology Managers.)

Carter wasn't around for all that development work—it's not the job of a scientist who's trying to explore new frontiers. These days, he's studying integrins for their role in facilitating the spread of cancer cells. If you could shut down this process, you might be able to stop tumors from spreading. That's what gets him excited now. "When you stop creating, you're not a scientist anymore," he says.

Still, Carter follows the news on natalizumab's ups and downs, and is clearly proud to have played a part in making this new medicine.

He's careful not to take too much credit for the years of work that ultimately made it into a marketed product. "I'm glad that a company had the foresight and the commitment to carry this to the market," Carter says. "To take a research tool and turn it into useful pharmaceutical, that's a big gamble." He adds that while in the midst of the work to identify integrins, he never foresaw how this basic science would be translated into such a big new drug. "We were pretty much clueless that it would have any clinical value," he says.


Go to Newer News Go to Older News