MS news and research
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More common than anyone suspects, the unspoken issue of sexual dysfunction affects more than half of the MS population.
Researchers delved into the private lives of men with multiple sclerosis (MS) in a recent study and discovered that sexual dysfunction is a common MS complication. Although it’s a topic patients may be reluctant to discuss with their neurologists, they should be aware that intimacy problems are often treatable.
Scientists from the Institute of Psychiatry and Neurology in Warsaw, Poland, interviewed 67 men with MS who were members of the National MS Center. The participants also filled out questionnaires and underwent neurological evaluations, all in an attempt to measure their sexual satisfaction.
Of those 67 men, researchers found that more than half complained of erectile dysfunction (ED), roughly a quarter reported decreased interest in sex or had issues reaching climax, and nearly a fifth had difficulty with ejaculation. These results didn’t seem to depend on the patient’s age, the amount of time since his diagnosis, or his level of disability.
A 'Wall of Silence'
The researchers concluded that sexual dysfunction "is highly prevalent but commonly overlooked in MS patients and has a significant impact on their sexual quality of life.” Despite these widespread issues, the researchers found that only 6 percent of the study participants had spoken about these problems with their doctor.
The discrepancy between the number of men who suffer from sexual dysfunction and those who report it to their doctor is probably due to the taboo nature of the topic.
Most likely, the subject doesn't come up, according to Megan Weigel, DNP, ARNP-C, MSCN, in an interview with Healthline, "because sexual dysfunction is a sensitive issue both for the person with the problem and the healthcare provider. However, it is possible that people with MS may not know it can be a symptom of the disease."
But if patients can put aside their discomfort long enough to have a frank conversation with their doctor—dropping the wall of silence—it may be possible to treat the problem.
Sexual Dysfunction Isn’t Just for Men
In an earlier study, the same group of researchers looked at sexual dysfunction in women with MS. While the researchers identified real issues faced by more than three quarters of the patients studied, only 2.2 percent of these women ever told their doctors about their sexual difficulties.
Among the problems women reported were lack of desire, decreased sensation in the genitals, poor lubrication, and an inability to climax. The study found that sexual dysfunction was "less likely in women who assessed their relationship positively but more common in older patients and those who had a positive history of depression.”
In the case of both male and female sexual dysfunction, the problem appears to be widely under-reported and overlooked by medical professionals.
Communication Is Key
MS is a disease that compromises the central nervous system, and sexual side effects are common among patients. Neurologists are trained to treat all aspects of the disease, including sexual complications. Understanding that it is a side effect of MS, and not due to any personal inadequacy, should quell the anxiety patients feel about discussing intimacy problems with their doctor.
The researchers stressed that neurologists should put more emphasis on sexual dysfunction when they examine their patients and have better screening tools in place. Doctors can treat problems only if they know symptoms exist, so, for patients, speaking up is imperative.
Sexual Dysfunction Defined
According to a 2009 article in MSFocus written by Frederick W. Foley, Ph.D., there are three types of MS-related sexual dysfunction: primary, secondary, and tertiary.
Primary dysfunction is caused by damage to the nerves from MS. Signals from the brain can no longer travel to parts of the body involved in sexual activity. Genital numbness is a classic example of primary dysfunction.
Examples of secondary dysfunction are bowel or bladder issues, spasticity or hand tremors—anything that indirectly complicates intimacy.
The tertiary variety of dysfunction is caused by the emotional aspects of MS—psycho-social or cultural issues that can impact a person’s feelings about sex. Body image, mood swings, and self-esteem can all affect intimacy. The changing dynamic of relationships—when life partners become caregivers, for example—can also play a role in tertiary sexual dysfunction.
Improving Sexual Quality of Life
Patients need not suffer in silence. "There are several ways to help men with MS who suffer from ED," Weigel said. "Medications like Viagra, Cialis, and Levitra may be helpful. If they are not, there are injectable medications and mechanical devices that may be required." For women, lubricants such as K-Y Jelly can help with vaginal dryness, and exploring new techniques for arousal might address loss of libido.
"Sexual dysfunction can be caused by side effects of medications like antidepressants, muscle relaxants, pain medications, and anti-seizure drugs; other medical conditions that affect small blood vessels, like diabetes and hypertension; and psychological issues, like loss, role changes, fear of failure, depression, and anxiety," Weigel said. "Timing of medication dosing, and timing of sexual activity so that it occurs at the time of day with the least fatigue can be helpful. Counseling and sex therapy are also very useful in conquering physical and emotional problems related to sexual dysfunction."
"Remember that as healthcare providers, we should be able to listen with a nonjudgemental, open ear in a nonthreatening environment to sensitive issues," Weigel added. She also suggests that patients write down their concerns and give the list to their doctor. "This could result in an open discussion that would put the person more at ease," she said.
Source: Healthline Copyright © 2005 - 2014 Healthline Networks, Inc (17/04/14)
Quantitative determination of regional lesion volume and distribution in children and adults with RRMS.
INTRODUCTION: Onset of MS occurs during childhood in about 5% of cases. It is unclear whether very young age at MS onset, when the nervous system is still myelinating, affects MS lesion accrual or regional distribution.
OBJECTIVE: To compare the frequency, volume and distribution of T2 and T1 lesions in children and adults with relapsing-remitting multiple sclerosis (RRMS).
METHODS: Lesions were segmented on T2- and T1-weighted MRI images from 29 children and 29 adults with RRMS, matched for disease duration.
RESULTS: All subjects exhibited T2-weighted brain lesions. Children had higher whole-brain T2-weighted-lesion-volume (T2LV) compared to adults (mean (SD) in cm(3): 12.76(2.7) vs. 10.03(3.4), p<0.0013). The supratentorial-T2LV was similar in children and adults (8.45(1.7) vs. 7.94(1.7), mean (SD), p?=?0.2582), but adults were more likely to have supratentorial lesions (96.5% vs. 68.9%, p<0.012). Children were more likely to have infratentorial-T2-weighted lesions (75.9% vs. 43.4%, p<0.03), specifically in the brainstem (62.1% vs. 26.7%, p<0.019) and the pons (48.3% vs. 17.24%, p<0.024), had higher infratentorial-T2-weighted-lesion counts (4.1(5.6) vs. 1.45(2.3), p<0.021), a greater infratentorial-T2LV (4.31(2.7) vs. 2.08(2.4), p<0.0013), and a greater infratentorial-T1-weighted-lesion-volume (T1LV) (3.7(2.5) vs. 1.08(1.9), p<0.0007). Whole-brain-T1LV was higher in children (9.3(2.5) vs. 6.43(2.1), p>0.001). Adult MS patients had higher supratentorial-T1LV (5.5(0.92) vs. 6.41(2.1), mean (SD), p<0.034), whereas children were more likely to have infratentorial-T1-weighted lesions (58.6% vs. 23.3%, p<0.015).
DISCUSSION: Onset of MS during childhood is associated with a higher volume of brain lesions in the first few years of disease relative to adults. Children with MS are more likely than adults to have T2 and T1 lesions in the infratentorial white matter, raising the possibility of preferential immune targeting of more mature myelin. Children with MS have a lower supratentorial T1 lesion burden, possibly reflecting more effective remyelination and repair in brain regions that are still engaged in active primary myelination.
Ghassemi R, Narayanan S, Banwell B, Sled JG, Shroff M, Arnold DL; Canadian Pediatric Demyelinating Disease Network.
Source: PLoS One. 2014 Feb 26;9(2):e85741. doi: 10.1371/journal.pone.0085741. eCollection 2014. & PMID: 24586244 (14/04/14)
BACKGROUND: Gonadal steroids may modulate disease course in multiple sclerosis (MS).
OBJECTIVE: To assess the prevalence and clinical associations of hypogonadism in men with MS.
METHODS: Male patients, aged 18-65 years, with relapsing-remitting MS (RRMS) or clinically-isolated syndrome (CIS) and their first symptom < 10 years prior were selected from a longitudinal clinical study. We measured their hormones in stored morning blood samples, and collected their Expanded Disability Status Scale (EDSS) scores every 6 months and their Symbol Digit Modalities Test (SDMT) results annually.
RESULTS: Our analysis included 96 men with a mean age of 40 years, EDSS of 1.1 and disease duration of 4.6 years. Of these men, 39% were hypogonadal (total testosterone < 288 ng/dL); none showed compensatory elevations in luteinizing hormone. Their low testosterone levels and testosterone:estradiol ratios were negatively correlated with body mass index (BMI) and leptin, and showed no correlation with 25-hydroxy-vitamin D levels. In our primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS (p = 0.044). In the age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with less decline in SDMT (p = 0.012).
CONCLUSIONS: Men with MS may experience hypogonadotropic hypogonadism. Low testosterone levels may be associated with worse clinical outcomes. A potential neuroprotective role for testosterone warrants further investigation.
Bove R, Musallam A, Healy B, Raghavan K, Glanz B, Bakshi R, Weiner H, De Jager P, Miller K, Chitnis T.
Source: Mult Scler. 2014 Apr 7. & Pubmed PMID: 24710799 (11/04/14)
Could MS be caused by a retrovirus?(10/04/14)
Could drugs shown to successfully treat HIV also be used to quell MS? To find out, researchers explore remnants of ancient viruses locked with the human genome.
Two new studies are under way to test antiretroviral medications on multiple sclerosis (MS) patients. This research is spurred by a narrowly accepted theory that MS may be triggered by human endogenous retroviruses.
In a phase-2 study currently enrolling volunteers, scientists at the Royal London Hospital in England will be following 24 patients who had been given the antiretroviral drug raltegravir, a therapy used to help prevent HIV-positive patients from developing AIDS.
Through a separate study, the Swedish company GeNeuro Innovation has developed a monoclonal antibody called GNbAC1, which targets a protein made by multiple-sclerosis–associated retrovirus (MSRV). GNbAC1 was tested on a small group of 10 patients with two different doses administered intravenously. If approved, it will become the first monoclonal antibody to target a retrovirus in MS. Patients on this drug would receive monthly IV infusions.
In 2003, scientists at the Human Genome Project completed the daunting task of mapping all of the genes found in human DNA. During that process, they discovered that nearly 8 percent of our DNA is composed of human endogenous retroviruses (HERVs), which, according to the National Institutes of Health (NIH), "represent footprints of previous retroviral infection and have been termed 'fossil viruses.'" HERVs are the remnants of the infections of our ancestors, passed on through our genes.
These leftover bits of DNA were originally thought to be harmless "garbage" that remained dormant. However, recent research has revealed that these HERVs can become reactivated, and may play a role in several autoimmune diseases and certain cancers. HIV and herpesviruses have been definitely linked to HERVs.
Epstein-Barr virus (EBV) has long been suspected as a possible MS trigger. EBV is a member of the herpesvirus family and, according to the NIH, nearly 95 percent of all people between the ages of 35 and 40 have been infected by it. Earlier studies have shown an increase in antigens to EBV in the blood of relapsing MS patients.
Several laboratories have isolated HERV proteins in MS patients, but this provides only circumstantial evidence of the role they might play in the disease. Although theories are beginning to emerge, even proponents of the idea don't know whether HERVs cause the disease or just create a “perfect storm” in which, once reactivated, they cause the immune system to overreact, triggering MS.
The HIV-MS Connection
Julian Gold, the director of the Albion Centre in Australia, specializes in treating HIV patients. After treating one patient in particular, Gold made an astonishing observation. In a 2011 case study done in collaboration with researchers at Royal London Hospital, he described a 26-year-old Australian man who had been diagnosed with both HIV and MS in 1985. Although HIV-positive, he still did not have AIDS by 1996, the year highly active antiretroviral therapy (HAART) was introduced.
Once Gold started the man on HAART to treat HIV, his MS symptoms disappeared. "Within months of commencing HAART, all MS symptoms gradually improved,” Gold and his colleagues explained in a letter published in the European Journal of Neurology, “Within 2 years, his urinary incontinence was controlled to the extent that he stopped wearing pads and fecal incontinence resolved. He has had no MS relapses."
Based on this observation, Gold wondered if perhaps a retrovirus similar to HIV might play a part in MS.
Evidence Is Growing
A 2012 study published in the Journal of Virology showed that components of a specific HERV were detected at higher levels in people with active MS.
“It is not yet known whether HERV components play a role in launching or worsening the immune attacks on the central nervous system in people with MS, or whether they are a result of those attacks,” the National MS Society wrote, in an article in about the study. “Further studies are required to address these and other questions about these intriguing findings, and their possible implications for people with MS or other disorders.”
While some researchers are skeptical about the retrovirus connection, others, such as Gold and his colleagues, feel it’s imperative to study the possible link if we want to explore all possible triggers for MS.
And since there is no animal model for HERVs in MS, studying them poses a challenge. "Their exact role will only be obtained following appropriate clinical trials,” argued Gold in an interview with MedPage Today. “If we wait for the laboratory to give us the answer, we will all have been retired."
Source: Healthline Copyright © 2005 - 2014 Healthline Networks, Inc (10/04/14)
Teva Pharmaceutical Industries Ltd has asked the U.S. Supreme Court to stop a lower court ruling from going into effect while the justices consider an appeal in a patent fight over Teva's top-selling multiple sclerosis drug Copaxone.
On March 31, the high court agreed to hear Teva's appeal of a July 2013 ruling by the U.S. Court of Appeals for the Federal Circuit in favor of two teams developing cheaper generic forms of Copaxone: one involving Novartis AG's Sandoz Inc and Momenta Pharmaceuticals Inc, and the other involving Mylan Inc and Natco Pharma Ltd.
The appeals court had upheld some of the nine patents involved in the drug, or portions of them, but declared several invalid, meaning patent protections were set to expire in May 2014 instead of September 2015.
The company's lawyers said in the court filing that if the appeals court ruling was not stayed, "Teva's innovative and widely prescribed treatment for multiple sclerosis will lose protection."
The Supreme Court will not be hearing oral arguments in the Teva case until its 2014 term begins in October. A ruling could come as late as June 2015. If the court does not act on the stay application, the ruling could come "effectively too late to prevent irreparable harm to Teva," the lawyers said.
The stay application was directed to Chief Justice John Roberts. He is likely to ask the other litigants for a response before deciding how to proceed.
Teva is currently trying to switch patients over to a new version of Copaxone, which is the company's most important product.
The case is Teva v. Sandoz, U.S. Supreme Court, 13-854.
Source: Reuters © Thomson Reuters 2014 (09/04/13)
In patients with multiple sclerosis, the body turns on itself, launching an immune system attack that destroys the coating around nerve fibers in the central nervous system, leaving them exposed like bare wires. Similar to exposed electrical lines, the unprotected fibers touch and short out, leading to the neurodegenerative effects that are a hallmark of multiple sclerosis.
But what if doctors could stop the immune response that destroys the protective coating before the disease becomes debilitating? University of Florida researchers have received a $40,000 grant from the National Multiple Sclerosis Society to test a gene therapy technique in mice that aims to help the body not treat itself like a foreign invader — a process referred to as immune tolerance — in the earliest stages of multiple sclerosis. If the researchers can re-establish this tolerance, they could thwart the immune system attack, all with a technique that could be used on a wide number of patients.
"In previous years, we have learned a lot about how to manipulate tolerance using gene therapy," said Brad E. Hoffman, Ph.D., an assistant professor of pediatrics in the UF College of Medicine. "Tolerance is your body's way of not responding to substances that would otherwise induce an immune response so you don't have an immune response to everything. In multiple sclerosis, the body loses that ability to distinguish between self and not-self so it starts to attack its own nervous system cells."
About 2.5 million people worldwide suffer from multiple sclerosis, according to the National Multiple Sclerosis Society. The disease typically causes problems with vision, fatigue, speech, sensation and mobility. In advanced cases, multiple sclerosis can lead to blindness and paralysis.
Typically, gene therapy is used to correct a faulty gene in the body. In this case, researchers will deliver a gene responsible for a brain protein into the liver, via the harmless virus AAV, in hopes that it will spark production of regulatory T cells. These T cells, which suppress the immune system, are crucial because they could effectively shut down the immune attack in the brain, Hoffman said. The researchers are injecting the gene specifically into the liver because the organ filters out unwanted immune responses.
"Everything filters through the liver for detoxification," Hoffman said. "Because of this, the liver has an innate capacity to induce immune tolerance. We have learned in other gene therapy studies that it is possible for the liver to make cells tolerant to the gene you are putting in."
Other research teams across the country are trying to spark immune tolerance to combat multiple sclerosis, too. However those studies involve developing treatments personalized for specific patients. The UF researchers' work is novel because they hope to develop a technique that could be used on a wide number of patients.
"Everyone has different types of T regulatory cells and receptors," Hoffman said. "By injecting a gene responsible for a brain protein, we are allowing an individual's body to make the specific T regulatory cells it needs.
"If it works, this is potentially more clinically feasible, cost-effective and translatable for a large scale."
Although gene therapy has yet to be used to correct autoimmune disorders such as multiple sclerosis, the foundations for the study are rooted in research Hoffman's team has performed while studying gene therapy for hemophilia. During these studies, the team was able to induce immune tolerance in mice, and Hoffman hopes the techniques will one day be able to help people with multiple sclerosis, too.
"Will we be able to cure MS? That would be ideal, but our strategy is more likely to result in suppressing the immune response to the nervous system," he said. "If you suppress the immune response, you will suppress the neurodegenerative effects and hopefully maintain a higher quality of life."
Source: South Florida Sun-Sentinel Copyright © 2014, South Florida Sun-Sentinel (09/04/14)
Nearly four months after the Food and Drug Administration rejected a multiple sclerosis drug developed by Genzyme, citing the clinical trial’s design and a risk of serious side effects, the Cambridge biotech said Monday that it will resubmit an application for approval to the agency.
Rather than appeal the FDA’s decision, as expected, Genzyme said it will file an updated license application for the drug candidate, called Lemtrada, in the second quarter. The new submission will specifically address issues raised by the FDA in its Dec. 27 decision turning down the experimental treatment, Genzyme said in a statement.
The move follows a series of discussions early this year between Genzyme executives and regulators in the neurology products division of the FDA’s Office of Drug Evaluation, said Genzyme spokeswoman Erin Walsh. She declined to elaborate on the talks and said company officials would not comment until after they resubmit their application. But she did say the drug maker has no plans to conduct additional clinical studies before the FDA rules.
“We had constructive discussions with the FDA that have led us down this path where we’re resubmitting our application rather than filing an appeal,” Walsh said. “We don’t believe further trials are needed prior to an approval. But we would entertain any kind of post-approval commitments” to the FDA, including possible further tests of the drug, she said.
Similarly, FDA officials would not talk about Genzyme’s plans to resubmit its Lemtrada application.
The agency rejected the drug for use in the United States, even though it had been approved by regulators in Europe, Canada, and Australia. The decision was criticised by MS patients, who said the drug had proven effective in clinical trials, and by investors who own a special class of stock that is tied to Lemtrada’s regulatory and sales milestones.
“We are not able to discuss any aspect of a drug application that is under agency review,” said FDA spokeswoman Sandy Walsh. In November, an FDA advisory committee warned that the drug’s side effects could include rashes, bleeding, and even thyroid cancer.
Genzyme scientists spent more than a decade developing Lemtrada for the treatment of multiple sclerosis, a disease that affects the central nervous system. About 1,700 patients were involved in clinical testing of the drug. More than 2.3 million people have been diagnosed with MS worldwide, including about 400,000 in the United States.
The potential of that market, and anticipation that Lemtrada would be approved in the United States, was a major attraction for the French drug maker Sanofi SA, which paid $20.1 billion to acquire Genzyme in 2011. In that deal, Sanofi agreed to reward former Genzyme stockholders if the drug achieved certain milestones in the US market.
Source: The Boston Globe © 2014 BOSTON GLOBE MEDIA PARTNERS, LLC (09/04/14)
Tecfidera is approved by Scottish Medicines Consortium for Scots with relapsing-remitting multiple sclerosis (07/04/14)
A NEW oral drug for people with relapsing-remitting multiple sclerosis is to be made available in Scotland.
Tecfidera (dimethyl fumarate) a first-line oral treatment could be an alternative to injectable medication for people with the most common form of multiple sclerosis (RRMS).
The drug which has been approved by the Scottish Medicines Consortium, 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.
Oral treatment Tecfidera approved by European Commission could benefit Scots living with relapsing remitting Multiple Sclerosis
James Overell, Consultant Neurologist, Institute of Neurological Sciences at the Southern General Hospital said: “Scotland has the highest prevalence of MS in the world, with more than 10,000 people living with MS in the country.
"The availability of Tecfidera expands the range of options for people with relapsing-remitting MS, and will be an attractive option both for newly diagnosed patients and for those patients previously treated with a self-injectable. It’s great that Scotland is leading the way in MS care by approving this new treatment.”
Dr Belinda Weller, Consultant Neurologist at the Western General Hospital, Edinburgh, “Scotland has the highest incidence of MS in the UK so I am delighted by the news that this new oral treatment, Tecfidera, has been approved by the Scottish Medicines Consortium for use in adults with relapsing remitting MS.
"Many of our patients have been waiting for it to become available. It is thought that Tecfidera works on two key areas of MS pathology - reducing inflammation and potentially also neuro-degeneration. Tecfidera provides a good option for patients wanting an effective and simple to use oral medication".
Source: www.dailyrecord.co.uk (07/04/14)
In final draft guidance, UK drugs watchdog the National Institute for Health and Care Excellence (NICE) has recommended the use of French drug major Sanofi (Euronext: SAN) subsidiary Genzyme’s multiple sclerosis drug Lemtrada (alemtuzumab).
The NICE is appraising alemtuzumab as a treatment for adults with relapsing–remitting multiple sclerosis, a chronic and disabling neurological condition that, as it progresses, can have a substantial negative impact on a person’s quality of life.
Currently available treatments for this type of MS are either oral daily tablets or injections given several times each week and can have unpleasant side effects. The NICE pointed out. Alemtuzumab is taken intravenously once a year for two years. The first course is administered for five consecutive days, and the second course is administered for three consecutive days, 12 months later allowing those with the condition to lead their lives without treatment for the rest of the time. Alemtuzumab does have some possible side effects associated with it which, according to clinical specialists, are manageable. Compared with most available treatments, alemtuzumab has a shorter time period during which it is not recommended that a person gets pregnant. This could be seen as advantageous for patients who are planning to have a baby.
Carole Longson, NICE Health Technology Evaluation Centre director, said: “We are very pleased to be able to recommend alemtuzumab for adults with relapsing-remitting multiple sclerosis. Following a request for more information by our independent Appraisal Committee, the manufacturer was able to provide further evidence, which has led to this positive recommendation.”
Until the NICE issues final guidance, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its guidance on a technology it replaces local recommendations across the country.
Pricing to be confirmed
The indicative price of alemtuzumab is £7,045 ($9,722) per 12 mg vial, which equates to £56,360 for the full course of treatment consisting of five daily consecutive 12mg doses in year one, followed by three daily consecutive 12mg doses 12 months later in year twp. The price of alemtuzumab has not yet been confirmed by the Department of Health. However, the Department has exceptionally agreed for this indicative price to be used for the purpose of this appraisal. Costs may vary in different settings because of negotiated procurement discounts.
Last year, when issuing draft guidance (The Pharma Letter December 5, 2013), Prof Longson said: “When reviewing the evidence for alemtuzumab, the Appraisal Committee concluded that there were still questions to be answered. This is why we have requested more details from the manufacturer; to ensure that we have the information the Appraisal Committee needs to reach their conclusions.”
Source: www.thepharmaletter.com (04/04/14)
A handful of people taking a medication called Rebif to treat multiple sclerosis have developed a serious condition that causes blood clots to form in small blood vessels throughout the body.
In a letter in the March 27 issue of the New England Journal of Medicine, Scottish researchers reported that they found an unexpectedly high number of cases of "thrombotic microangiopathy" in people taking Rebif who suddenly developed severe high blood pressure. The condition is a combination of the clotting disorders hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura (HUS/TTP).
The two disorders often occur together. In HUS, the red blood cells are destroyed, and the debris from that destruction clumps together and clots. Those numerous blood clots cause TTP, which occurs when small blood vessels throughout the body become blocked with blood clots, according to the U.S. National Library of Medicine.
The clotting condition is a recognised complication of using Rebif, which is one of the brand names for the drug interferon beta 1-alpha, said study senior author Siddharthan Chandran, a professor of neurology at the University of Edinburgh. In fact, British regulatory authorities issued a drug-safety update last December on the heightened risk for the condition, Chandran added.
While Chandran said that Merck, the maker of Rebif, has stated in product labeling that this clotting condition is rare, the researchers suggest that some recent change in the manufacturing process might play a role because these complications haven't been seen thus far in another type of interferon beta 1-alpha.
Two U.S. experts weighed in on the issue.
"The National MS Society's expectation is that regulatory authorities will look into the matter cited in the NEJM letter to determine if there are any additional safety concerns beyond the cautions that already appear on the product's label," said Timothy Coetzee, chief advocacy, services and research officer for the National MS Society.
Dr. Karen Blitz, director of the North Shore-LIJ Multiple Sclerosis Center in East Meadow, N.Y., said medications all have some risks, even aspirin. In this case, she said, "the risk-benefit profile for this drug is still way in favor of the benefits. People with MS who aren't protected by disease-modifying therapy have a higher likelihood of disability."
Interferon beta 1-alpha is believed to help slow the progression of MS if it is given early in the course of the disease and taken long-term. It's what is known as a disease-modifying drug.
In the first nine years of safety monitoring of Rebif, there were very few cases of the dangerous clotting condition, according to background information in the letter. However, the number of cases has been increasing recently and it's not clear why.
"The mechanism that triggers this complication is not fully understood, and more research is needed into the relationship between interferon beta and thrombotic microangiopathy," noted Chandran.
What the researchers did learn from the four cases of the clotting condition that they studied was that all of the patients had been taking Rebif for years and tolerated the drug well. All of the patients had severe high blood pressure when they sought treatment for the blood complication.
In reviewing past medical records, the researchers found that three of the four had been newly diagnosed with high blood pressure. The patients also showed abnormalities in their blood, and impaired kidney function in the months before developing the clotting condition, according to the letter.
"Our findings suggest that unexplained high blood pressure and abnormalities of blood count and kidney function may well be early warning signs of this complication," said Chandran.
Blitz added that patients also need to be vigilant.
"Anyone taking medication for MS should be monitored regularly by a physician. But, people still have to watch their body and address any changes in the way you're feeling with your doctor," Blitz advised.
"This complication is very rare, and the risk is small," she said, adding that the regular follow-up appointments and blood work may help reduce the risk even more by catching any changes early on.
Chandran said the bottom line is that "doctors and patients should be aware that this is a recognised complication of Rebif. There is an opportunity to reduce the risk from this complication by increased awareness of the complication and detection of early warning signs."
After being asked whether this complication is a concern in the United States, a U.S. Food and Drug Administration spokeswoman told HealthDay News that the agency is aware of the issue but has no further comment at this time.
SOURCES: Siddharthan Chandran, Ph.D., professor, neurology, University of Edinburgh, Scotland; Timothy Coetzee, Ph.D., chief advocacy, services and research officer, National MS Society; Karen Blitz, D.O., director, North Shore-LIJ Multiple Sclerosis Center, East Meadow, N.Y.; March 27, 2014, New England Journal of Medicine
Source: Copyright (c) 2014 HealthDay. All rights reserved. (04/04/14)
Translational Biosciences, a subsidiary of Medistem Panama, has received the green light for a phase I/II clinical trial using human umbilical cord-derived mesenchymal stem cells (UC-MSC) for multiple sclerosis from the Comité Nacional de Bioética de la Investigación (CNEI) Institutional Review Board (IRB) in Panama.
According to the US National Multiple Sclerosis Society, in Multiple Sclerosis (MS), an abnormal immune-mediated T cell response attacks the myelin coating around nerve fibers in the central nervous system, as well as the nerve fibers themselves. This causes nerve impulses to slow or even halt, thus producing symptoms of MS that include fatigue; bladder and bowel problems; vision problems; and difficulty walking. The Cleveland Clinic reports that MS affects more than 350,000 people in the United States and 2.5 million worldwide.
Mesenchymal stem cells harvested from donated human umbilical cords after normal, healthy births possess anti-inflammatory and immune modulatory properties that may relieve MS symptoms. Because these cells are immune privileged, the recipient’s immune system does not reject them. These properties make UC-MSC interesting candidates for the treatment of multiple sclerosis and other autoimmune disorders.
Each patient will receive seven intravenous injections of UC-MSC over the course of 10 days. They will be assessed at 3 months and 12 months primarily for safety and secondarily for indications of efficacy.
The stem cell technology being utilised in this trial was developed by Neil Riordan, PhD, founder of Medistem Panama. The stem cells will be harvested and processed at Medistem Panama’s 8000 sq. ft. ISO-9001 certified laboratory in the prestigious City of Knowledge. They will be administered at the Stem Cell Institute in Panama City, Panama.
From his research laboratory in Dallas, Texas, Dr. Riordan commented, “Umbilical cord tissue provides an abundant, non-controversial supply of immune modulating mesenchymal stem cells. Preclinical and clinical research has demonstrated the anti-inflammatory and immune modulating effects of these cells. We look forward to the safety and efficacy data that will be generated by this clinical trial; the first in the western hemisphere testing the effects of umbilical cord mesenchymal stem cells on patients with multiple sclerosis.”
The Principle Investigator is Jorge Paz-Rodriguez, MD. Dr. Paz-Rodriguez also serves as the Medical Director at the Stem Cell Institute. For detailed information about this clinical trial visit http://www.clinicaltrials.gov.
Source: PR Web ©Copyright 1997-2014, Vocus PRW Holdings, LLC (03/04/14)
Antisense Therapeutics Limited is pleased to advise that results from a chronic toxicity study in monkeys indicate that ATL1102, an antisense oligonucleotide currently under development for the treatment of multiple sclerosis (MS), was well-tolerated when given subcutaneously for a 6-month dosing period at the 2 dose levels tested (1.5 and 3mg/kg/dose). The Company believes that the preclinical and clinical experience to date with ATL1102 should allow dosing in future trials at or above the 1.5 mg/kg/dose level.
Based on histologic findings in common with a previous monkey study at doses exceeding 1.5mg/kg/dose, the Company continues to evaluate the chronic monkey data with regard to potential human relevance, and safety biomarkers that may be useful in future clinical studies. Exposures achieved in this study are regarded as potentially clinically relevant based on the efficacy outcomes from the previously conducted Phase IIa trial of ATL1102 in MS patients.
Pending receipt and final data evaluation from the current study, as well as review of all the preclinical and clinical data obtained, ANP is planning future regulatory agency discussions regarding further development of ATL1102 and the dosing regimen for a future Phase IIb trial in MS patients. The Company anticipates final review of the data by June this-year and follow-up discussions with the US Food and Drug Administration (FDA) at a pre-IND meeting during the 3rd quarter 2014.
Antisense Therapeutics CEO and Managing Director Mark Diamond said “The results of this most recent toxicology study and the human data to date are encouraging and re-ignite our hopes for this project. We are continuing to generate new data on ATL1102 which we believe will support positive interactions with the FDA in relation to our plans for a future Phase IIb trial in MS patients. We look forward to confirming our plans for the further clinical development of ATL1102 with the FDA in the coming months.”
Source: www.news-medical.net/ (02/04/14)
As the world’s largest maker of generic drugs, Teva Pharmaceutical Industries has been critical of brand-name manufacturers that try to block generic versions of their high-priced medicines.
But Teva is now emulating its rivals, mounting an aggressive effort to stave off generic versions of Copaxone, its big-selling brand-name drug for multiple sclerosis, which is set to lose patent protection late in May.
On Monday, Teva got help from the United States Supreme Court, which agreed to hear its appeal of a lower-court ruling that invalidated a patent that would have protected Copaxone until September 2015.
Teva, based in Israel, is desperate to stave off generic competition to Copaxone, which had global sales last year of $4.3 billion; $3.2 billion of that figure came from the United States. The drug, which has been on the market for 17 years and is the best-selling treatment for M.S., accounts for about 20 percent of Teva’s revenue and about half its profit.
But a generic version of Copaxone could provide needed cost relief to the health care system. The list prices of Copaxone and other older M.S. drugs have roughly quadrupled over the last decade, to about $60,000 a year.
“The prices would go up 10, 20, 30 percent at a time for no apparent reason,” said Dr. John R. Corboy, co-director of the Rocky Mountain Multiple Sclerosis Center at the University of Colorado. “We spend a quarter, some days half our time talking to patients about insurance and figuring out how we are going to get them medications.”
At the same time, Teva has been frantically trying to convert patients to a new, more concentrated form of Copaxone that requires patients to inject themselves only three times a week instead of every day. That new form would not be subject to generic competition. Once patients convert, it would be harder for insurers to force them to use a generic that would require them to go back to daily injections.
Teva has also submitted one petition after another to the Food and Drug Administration claiming, in essence, that Copaxone has such a complex makeup that it is virtually impossible to demonstrate that a copy is the same as the original. Subtle differences could make a generic less effective or even dangerous.
Ten years ago, Aventis, now part of Sanofi, made the same complexity argument about its blood thinner Lovenox.
In that case, Teva was on the other side, trying to introduce a generic. It accused Aventis of “blatant and unjustified efforts” to deny consumers “the cost savings associated with robust and fair generic competition.” The F.D.A. approved Teva’s generic.
Teva says Copaxone, which is known generically as glatiramer acetate, is more complex than Lovenox. It rejected suggestions it was being hypocritical in trying to block generic versions of Copaxone.
“I think it would be hypocritical if there would not be quality and efficacy and safety issues for patients here,” Dr. Robert Koremans, president of Teva’s specialty medicines division, said in an interview.
Copaxone is made up of four amino acids linked in chains of various sizes and sequences. It is not clear how the drug works, but it does reduce the frequency of M.S. relapses. The disease results from attacks on the protective covering of nerves by the body’s own immune system, causing symptoms like blurred vision and difficulty walking.
The F.D.A. has not yet approved a generic version of Copaxone, perhaps because of its complexity. But two teams have said they are confident the agency will approve their drugs as early as May. One team consists of Momenta Pharmaceuticals and Sandoz, the generic arm of Novartis. The other is Mylan and Natco Pharma.
The companies declined to comment Monday on whether they would still start selling their drugs given the Supreme Court’s decision to hear Teva’s appeal. But Craig A. Wheeler, the chief executive of Momenta, said last week that it “shouldn’t change things in my view.”
Sailesh K. Patel, an intellectual property lawyer in Chicago who is not involved in this case, said the generic companies could face damages if they market their products now and Teva ultimately prevails.
Even if the generics get to market by late May, Teva hopes by then to have converted 30,000 of the roughly 85,000 American Copaxone users to the new version of Copaxone, which was approved by the F.D.A. in late January.
To do that, Teva has expanded the staff of its patient support operation, Shared Solutions. The organization has made “thousands of phone calls” to patients and doctors, Dr. Michael Hayden, Teva’s chief scientific officer, said at an investor conference in late February.
Shared Solutions has also been holding complimentary dinners for patients. Two patients who attended a buffet dinner at a Mexican restaurant in Downey, Calif., on Thursday said they would switch to the new Copaxone, enticed by having only three injections a week.
“I just signed my paper right now,” said one of them, who gave her name only as Linda A.
Teva has set the price of the new Copaxone at $4,641 a month, lower than the older, daily version, which costs $5,060 monthly.
The conversion is “nicely ahead of plan,” Dr. Koremans said.
But there is some resistance. Excellus BlueCross BlueShield in upstate New York is requiring that a switch to the new Copaxone be medically necessary, not just for convenience. It hopes to keep patients on the daily version so their prescriptions would be automatically switched to a generic, saving employers money.
In six petitions to the F.D.A. since 2008 Teva has said, among other things, that generics should not be approved without clinical trials, something not usually required.
Synthon, a Dutch company that is developing a generic, just completed such a trial showing its drug was as good as Copaxone in reducing brain lesions. Synthon says European regulators want such trials. But the F.D.A. has not required them.
Source: The New York Times © 2014 The New York Times Company (01/04/14)
AAN endorses cannabis for MS(27/03/14)
The American Academy of Neurology has issued new evidence-based complementary and alternative medicine guidelines for multiple sclerosis.
HealthDay News -- The American Academy of Neurology is recommending oral cannabis extract to help ease spasticity symptoms and pain in patients with multiple sclerosis, along with other therapies, in new evidence-based complementary and alternative medicine (CAM) recommendations.
Vijayshree Yadav, MD, of the Oregon Health & Science University in Portland, and other members of the AAN's Guideline Development Subcommittee, conducted a literature search to develop the recommendations, which are published online in Neurology.
Clinicians may offer oral cannabis extract (Level A) or tetrahydrocannabinol (Level B) for spasticity symptoms and pain (excluding central neuropathic pain), but should counsel patients that these agents are probably ineffective for objective spasticity (short-term)/tremor (Level B) and possibly effective for spasticity and pain (long-term; Level C).
Sativex oromucosal cannabinoid spray (nabiximols) can be suggested for spasticity symptoms, pain and urinary frequency (Level B), but clinicians should counsel patients that these agents are probably ineffective for objective spasticity/urinary incontinence (Level B). Furthermore, the spray is not currently FDA-approved and is unavailable in the United States, the researchers noted.
"In the United States, caution should be exercised with regard to extrapolation of results of trials of standardized oral cannabis extracts (which are unavailable commercially) to other nonstandardized, nonregulated cannabis extracts (which may be commercially available in states with medical marijuana laws)," Yadav and colleagues wrote.
Magnetic therapy is probably effective for fatigue, but probably ineffective for depression (Level B). Among common supplements, clinicians can counsel patients that fish oil is probably ineffective for relapses, disability, fatigue, magnetic resonance imaging lesions, and quality of life (Level B). Ginkgo biloba is ineffective for cognition (Level A), but possibly effective for fatigue (Level C). Reflexology is possibly effective for paresthesia (Level C).
Possibly ineffective therapies (Level C) include Cari Loder for disability, depression and fatigue, and bee sting therapy for relapses, disability, fatigue and lesion burden/volume.
"Clinicians should exercise caution regarding standardized versus nonstandardized cannabis extracts and overall CAM quality control/nonregulation," the researchers wrote. "Safety/efficacy of other CAM/CAM interaction with MS disease-modifying therapies is unknown."
Reference 1.Yadav V et al. Neurology. 2014; 82(12): 1083-1092.
Source: Copyright © 2014 Haymarket Media, Inc. All Rights Reserved (27/03/14)
Synthon announces successful outcome of the Phase III GATE study with its generic glatiramer acetate(27/03/14)
NIJMEGEN, the Netherlands--(BUSINESS WIRE)--Synthon today announced that the company’s glatiramer acetate met the main endpoint of a late-stage study in patients with relapsing remitting multiple sclerosis (RRMS). The Phase III Glatiramer Acetate clinical trial To assess Equivalence with Copaxone®* (GATE) is to-date the only Phase III study conducted with a generic version of Copaxone® and has demonstrated an equivalent efficacy and safety profile for Synthon’s glatiramer acetate compared to Copaxone®.
GATE was set up following Scientific Advice received from the European Medicines Agency (EMA) with the aim to show equivalence of Synthon’s glatiramer acetate (Synthon GTR) with Teva’s Copaxone® in a well-controlled 3-arm double-blind study that was also designed to show superiority of the two active treatment groups over placebo. The large-scale, multicenter study consists of a nine-month double-blind efficacy comparison followed by a currently ongoing 15-month open-label extension and runs in Europe (including Russia, Ukraine and Belarus), Mexico, South Africa and the United States. “The data gathered during the double-blind part of the study present a solid basis for the regulatory submission in Europe in order to make an equivalent alternative to Copaxone® available to patients suffering from multiple sclerosis”, commented Jacques Lemmens, Synthon’s chief executive officer.
In the GATE study 796 patients with active RRMS were randomized to daily injections of Synthon’s glatiramer acetate (20 mg/ml), Copaxone® (20 mg/ml) or matching placebo for a double-blind 9-month treatment period. Primary endpoint of the study was the number of T1 gadolinium enhancing brain lesions on MRI assessed after 7, 8 and 9 months of treatment which were convincingly shown to be equally reduced in both the Synthon GTR as well as the Copaxone® treatment groups and significantly reduced compared to placebo. Other outcomes, including the incidence of MS relapses, disability, and patient reported tolerability, support the primary conclusion of the study. Safety analyses showed a comparable incidence of reported adverse reactions between both active glatiramer acetate groups.
Following the double-blind phase of the trial, patients in the Copaxone® and placebo groups of the GATE study switched over to Synthon GTR and are continuing Synthon GTR treatment for another 15-month period, as are the patients in the Synthon GTR arm of the study. This part of the study is expected to further confirm efficacy and safety of long-term Synthon GTR treatment as well as to provide evidence supporting the safety of switching therapies from Copaxone® to Synthon’s GTR. Jeffrey Cohen, M.D., Professor in the Cleveland Clinic Lerner College of Medicine, Director of Experimental Therapeutics at the Cleveland Clinic Mellen MS Center, and Chair of the GATE Steering Committee, remarked that “these are important results. The mechanism of action of Copaxone® is not fully understood and the resulting complexity of developing a generic alternative/version is broadly acknowledged. Clinically proven equivalence will ensure that patients with multiple sclerosis are provided with an effective and safe alternative.”
Concludes Lemmens: “Glatiramer acetate is the first anticipated generic version of an approved MS product in the United States and the European Union. The future availability of a generic of Copaxone® means that MS treatments – which currently cost between USD 30,000-60,000 per patient per year – will become more affordable, thereby allowing more MS patients around the world to have access to this medication.”
Full details of the study will be submitted for publication in a peer-reviewed medical journal and presented at future scientific meetings.
Synthon has already submitted an Abbreviated New Drug Application (ANDA) for glatiramer acetate, 20 mg/ml solution for injection in pre-filled syringes to the United States FDA in November 2011.
*Copaxone® is a registered trademark of Teva Pharmaceutical Industries Ltd.
Source: ©2014 Business Wire (27/03/14)
Researchers report drug mobilises a kind of cell easily infected by a virus that attacks the brain.
Researchers report that they think they have figured out why patients who take the multiple sclerosis drug Tysabri face a high risk of developing a rare, and sometimes fatal, brain infection.
A common virus that can cause the brain disease progressive multifocal leukoencephalopathy (PML) likes to infect and hide in certain blood cells that are triggered to mobilise by Tysabri, the study authors explained. Even more troubling, the researchers discovered that current tests may be missing some who harbour the virus.
"Right now, the risk of PML in patients treated with [Tysabri] for more than two years is about one in 75 patients. That's a very high risk," said study author Eugene Major, a senior investigator at the U.S. National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md.
"We need to be able to understand why this therapy puts patients at risk. As we further define that, we'll be able to develop better tests and better treatment decisions can be made," Major said.
In PML, the normally harmless "JC virus" attacks the white matter of the brain, stripping nerve cells of their insulation. Without this insulation, nerve cells can't effectively carry brain signals. The disease causes progressive weakness, paralysis, changes in vision and speech, and problems with thinking and memory.
According to the NINDS, 30 percent to 50 percent of patients with PML die within a few months of diagnosis. Those who survive the infection may face permanent disability.
Though most people carry the JC virus, PML is rare. It tends to strike people with suppressed immune function, such as patients with AIDS or those taking powerful immune-suppressing drugs like Tysabri.
The drug has had a troubled history. First approved by the U.S. Food and Drug Administration in November 2004, it was pulled off the market three months later after cases of PML occurred in ongoing clinical trials.
Since Tysabri was allowed back on the U.S. market in 2006 with strict prescribing conditions, more than 440 cases of PML have been reported in patients taking the drug, according to the study background. In 2010, the FDA added a warning about the heightened risk of PML to the drug's labeling.
A combination of three factors seems to put patients at highest risk: treatment with Tysabri for more than two years; receiving other kinds of immune-suppressing medications; and testing positive for antibodies to the JC virus.
To find out why the drug carries such a high risk of PML, researchers collected blood samples from two groups of MS patients -- those just starting treatment with Tysabri, and those who had been on the drug for more than two years. They compared those samples to blood taken from healthy volunteers.
The investigators were looking for a particular type of cell in the blood -- a kind of stem cell that turns into white blood cells called B-cell lymphocytes.
"Turns out in these MS patients treated with [Tysabri], the number of these blood stem cells is three- to 10-fold higher than you'd see normally under normal physiologic conditions," Major said.
"JC virus is able to infect these blood stem cells as they become a B lymphocyte," he explained. His working theory has been that these infected B lymphocytes then carry the infection into the brain.
To test that theory, the researchers wanted to see if they could find traces of the JC virus in circulating blood stem cells.
And they did. Of 26 patients who were just starting treatment with Tysabri, 50 percent had traces of the JC virus in their circulating blood stem cells. Of 23 patients who had taken the drug for more than two years, 44 percent had JC virus DNA in more than one kind of blood stem cell type. In contrast, only 17 percent of the 18 healthy volunteers had signs of the JC virus in those cells.
"It was somewhat surprising to us that quite a high percentage of individuals had detectable viral DNA in these blood stem cells," Major said.
But what isn't exactly clear is how this could affect their risk of developing PML. Most patients who tested positive for JC virus had only a few copies of the virus, suggesting that they were still at low risk of infection. Patients who had taken the drug for more than two years had higher virus counts than those who were just starting treatment.
"We need to look at additional patients, and follow them for a long period of time," Major said.
Perhaps most concerning, 10 study participants had evidence of the JC virus in their blood but tested negative for antibodies to it. That suggests current tests for the virus may be missing some patients who could be at high risk for PML infection, the authors explained.
An expert who was not involved in the study, which was published online March 25 in the journal JAMA Neurology, said the findings left some questions unanswered.
"Clearly, Tysabri seems to engender the release of JC virus-containing cells from the bone marrow," said Dr. Gary Birnbaum, a neurologist and director of the Multiple Sclerosis Treatment and Research Center in Golden Valley, Minn. "This could explain why risks of PML are high in patients on this drug," he noted.
"What isn't clear is why the risk escalates dramatically after two years, since JC virus-bearing cells emerge early in the course of treatment," Birnbaum pointed out.
Additionally, Birnbaum said it was "disquieting" that researchers found evidence of the JC virus in patients who then tested negative for antibodies to it.
"Thus, testing individuals for exposure to JC virus by measuring antibodies to the virus may be insufficient to fully assess their risks for developing PML," he said.
Source: WebMD ©2005-2014 WebMD, LLC (26/03/14)
ANVISA, Brazil’s national health surveillance agency, has approved Sanofi company Genzyme's Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS) to slow or reverse the accumulation of physical disability and reduce the frequency of clinical exacerbations.
Lemtrada is supported by a clinical development program that involved about 1,500 patients and 5,400 patient-years of follow-up.
The approval in Brazil follows the recent approvals of Lemtrada in Mexico, Canada, Australia and the European Union (EU).
The company said that lemtrada is currently not approved in the US.
In December 2013, the company secured a complete response letter from the US FDA on its application for US approval of Lemtrada and announced its intent to appeal this decision. Marketing applications for Lemtrada are also under review in other countries.
Brazil's Hospital da Restauração head of Neurology Maria Lucia Brito Ferreira said lemtrada is an new treatment, with clinical trial data that support its potential to meaningfully address relapse rates and disability in patients with active MS.
"Lemtrada will provide physicians with a promising new option for their patients with active MS and could change the way this disease is managed," Ferreira said.
The company said that Lemtrada 12mg has a new dosing and administration schedule of two annual treatment courses.
The first treatment course of Lemtrada is administered through intravenous infusion on five consecutive days, and the second course is given on three consecutive days, 12 months later.
Most common side effects of Lemtrada are infusion associated reactions, infections, lymphopenia and leukopenia.
Source: © PBR 2010. Part of Progressive Digital Media Group Plc (24/03/14)
Researchers tested the compound in mice that had a condition in which the immune system tries to eliminate foreign cells.
Oregon State University scientists have discovered a chemical compound that could be a safer alternative to treating autoimmune diseases, possibly bringing hope to people suffering from conditions caused by their immune system attacking their bodies.
Studies are still needed in humans, however. Autoimmune diseases can affect almost any part of the body and result in such diseases as colitis, multiple sclerosis and psoriasis.
“We mostly treat autoimmune diseases with high-dose corticosteroids or cytotoxic drugs to suppress the immune response, and the side effects can be very difficult to deal with,” lead researcher Nancy Kerkvliet said in a statement. “But if this chemical works in clinical studies, it could result in a safer alternative to conventional drugs.”
Kerkvliet and OSU professor Siva Kumar Kolluri tested thousands of chemical compounds and found that one of them, 10-CI-BBQ, binds to a protein inside T cells. The chemical and protein pass into the nucleus and change the cells into regulatory T cells, which shut down the immune response.
Researchers tested the compound in mice that had a condition in which the immune system tries to eliminate foreign cells. The disease can occur in humans when they receive stem cell or bone marrow transplants.
Daily injections completely suppressed the disease. The compound was rapidly metabolized and not toxic.
The research was published in the journal PLOS ONE.
Source © 2014 American City Business Journals. All rights reserved. (21/03/14)
Stem cells derived from human muscle tissue were able to repair nerve damage and restore function in an animal model of sciatic nerve injury, according to researchers at the University of Pittsburgh School of Medicine. The findings, published online today in the Journal of Clinical Investigation, suggest that cell therapy of certain nerve diseases, such as multiple sclerosis, might one day be feasible.
To date, treatments for damage to peripheral nerves, which are the nerves outside the brain and spinal cord, have not been very successful, often leaving patients with impaired muscle control and sensation, pain and decreased function, said senior author Johnny Huard, Ph.D., professor of orthopaedic surgery, and Henry J. Mankin Chair in Orthopaedic Surgery Research, Pitt School of Medicine, and deputy director for cellular therapy, McGowan Institute for Regenerative Medicine.
"This study indicates that placing adult, human muscle-derived stem cells at the site of peripheral nerve injury can help heal the lesion," Dr. Huard said. "The stem cells were able to make non-neuronal support cells to promote regeneration of the damaged nerve fiber."
The researchers, led by Dr. Huard and Mitra Lavasani, Ph.D., first author and assistant professor of orthopaedic surgery, Pitt School of Medicine, cultured human muscle-derived stem/progenitor cells in a growth medium suitable for nerve cells. They found that, with prompting from specific nerve-growth factors, the stem cells could differentiate into neurons and glial support cells, including Schwann cells that form the myelin sheath around the axons of neurons to improve conduction of nerve impulses.
In mouse studies, the researchers injected human muscle-derived stem/progenitor cells into a quarter-inch defect they surgically created in the right sciatic nerve, which controls right leg movement. Six weeks later, the nerve had fully regenerated in stem-cell treated mice, while the untreated group had limited nerve regrowth and functionality. Twelve weeks later, treated mice were able to keep their treated and untreated legs balanced at the same level while being held vertically by their tails. When the treated mice ran through a special maze, analyses of their paw prints showed eventual restoration of gait. Treated and untreated mice experienced muscle atrophy, or loss, after nerve injury, but only the stem cell-treated animals had regained normal muscle mass by 72 weeks post-surgery.
"Even 12 weeks after the injury, the regenerated sciatic nerve looked and behaved like a normal nerve," Dr. Lavasani said. "This approach has great potential for not only acute nerve injury, but also conditions of chronic damage, such as diabetic neuropathy and multiple sclerosis."
Drs. Huard and Lavasani and the team are now trying to understand how the human muscle-derived stem/progenitor cells triggered injury repair, as well as developing delivery systems, such as gels, that could hold the cells in place at larger injury sites.
Mitra Lavasani, Seth D. Thompson, Jonathan B. Pollett, Arvydas Usas, Aiping Lu, Donna B. Stolz, Katherine A. Clark, Bin Sun, Bruno Péault, Johnny Huard. Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI44071
Source: Science Daily Copyright 2014 by ScienceDaily, LLC (20/03/14)
Australia’s Therapeutic Goods Administration (TGA) revealed today that it is monitoring reports of melanoma in patients being treated with natalizumab and encourages consumers and health professionals to report all such cases.
Natalizumab, Biogen Idec’s blockbuster drug Tysabri, which generated global in-market sales of $1.7 billion last year) is used to treat patients with relapsing-remitting multiple sclerosis to delay the progression of physical disability and reduce the frequency of relapse.
Melanoma is potentially life-threatening and Australia has one of the highest incidence rates of this condition in the world.Three cases of melanoma in patients being treated with natalizumab have been reported to the TGA.
An ongoing TGA review of this issue has found insufficient evidence to show a definite link between natalizumab and melanoma. However, given the high incidence of melanoma in Australia, this remains an issue of concern for the TGA.
Source: The Pharma Letter © The Pharma Letter Limited 2014 (19/03/14)
The US Food and Drug Administration has extended the initial Prescription Drug User Fee Act (PDUFA) date for its review of US biotech firm Biogen Idec’s Biologics License Application for Plegridy (peginterferon beta-1a), a subcutaneous pegylated interferon candidate for relapsing forms of multiple sclerosis (RMS).
The PDUFA date has been extended by three months, which is the standard extension period. The FDA has indicated that the extension of the PDUFA date is required to allow additional time for review of the application. The agency has not asked for additional studies, noted Biogen Idec.
Regulatory authorities in the USA and the European Union accepted the marketing applications for the review of Plegridy in RMS last year. Assuming that Plegridy comes to the market, it will add to Biogen Idec’s already strong MS franchise, which includes one of the leading drugs in the sector, Tysabri (natalizumab), as well as Avonex (interferon beta 1a) and more recently approved Tecfidera (BG-12, dimethyl fumarate), which many analysts have said could become the leading treatment for MS.
Source: The Pharma Letter © The Pharma Letter Limited 2014 (19/03/14)
A team of biologists and engineers at the University of California, San Diego has discovered that white blood cells, which repair damaged tissue as part of the body's immune response, move to inflamed sites by walking in a stepwise manner. The cells periodically form and break adhesions mainly under two "feet," and generate the traction forces that propel them forward by the coordinated action of contractile proteins. Their discovery, published in the Journal of Cell Biology, is an important advance toward developing new pharmacological strategies to treat chronic inflammatory diseases such as arthritis, irritable bowel syndrome, Type 1 diabetes, and multiple sclerosis.
"The immune system requires the migration of white blood cells to the point of infection and inflammation to clear invaders and begin the process of digesting and repairing tissue. However, when the body fails to properly regulate the recruitment of these cells, the inflammation can become chronic resulting in irreversible tissue injury and loss of functionality," said Juan C. Lasheras, a professor in the departments of Mechanical and Aerospace Engineering and Bioengineering, and in the Institute for Engineering in Medicine. "Understanding the way in which these cells generate the necessary forces to move from the blood stream to the site of inflammation will guide the design of new strategies that could target specific mechanical processes to control their migration," Lasheras said.
Figuring out how white blood cells move required an interdisciplinary approach involving engineering and biological sciences. The lead author of the study is Effie Bastounis, a member of a team led by UC San Diego Jacobs School of Engineering professors Lasheras and Juan Carlos del Alamo, of the Department of Mechanical and Aerospace Engineering, and Richard A. Firtel, a professor of Cell and Developmental Biology in the Division of Biological Sciences. "This work was made possible through interdisciplinary approaches that applied mathematical tools to a basic question in cell biology about how cells move," stated Richard Firtel. "By first applying novel methodologies to study the amoeba Dictyostelium, an experimental system often used by cell biologists, we were able to discover the basic mechanisms that control amoeboid movement, which we then applied to understanding white blood cells."
The team used new analytical tools to measure, with a high degree of accuracy and resolution, the forces the cells exert to move forward. The novel methodology, which they have been refining during the last several years supported by grants from the National Institutes of Health (R01-GM084227 and R01-GM037830), is called Fourier Traction Force Microscopy. Before their study, scientists thought white blood cells did not move in a highly coordinated manner. Furthermore, their work discovered that cells move by not only extending themselves at their front and contracting their backs, but also by squeezing inwardly along their lateral sides pushing the front of the cell forward. These findings establish a new paradigm as to how cell move. The research team is currently extending their techniques, which they have used to study leukocytes and other types of amoeboid cells, to investigate the mechanics of cancer cell migration and invasion.
Source: MNT © 2004-2014 MediLexicon International Ltd (19/03/14)
Assessment of cancer risk with β-interferon treatment for multiple sclerosis.
OBJECTIVE: The risk of cancer after exposure to the β-interferons (IFNβs) for multiple sclerosis (MS) has not been established. We assessed whether IFNβ treatment for MS is associated with cancer risk or the risk of specific cancers in a population-based observational study.
METHODS:The British Columbia MS database was linked to the provincial Cancer Registry, Vital Statistics death files and Health Registration files. Using a nested case-control design, MS cancer cases were matched with up to 20 randomly selected MS controls at the date of cancer diagnosis by sex, age (±5 years) and study entry year using incidence density sampling. Associations between treatment exposure and overall or specific (breast, colorectal, lung and prostate) cancers were estimated, adjusted for MS disease duration and age. Tumour size at cancer diagnosis was compared between treated and untreated patients.
RESULTS: The cohort included 5146 relapsing-onset MS patients and 48 705 person-years of follow-up, during which 227 cancers were diagnosed. Exposure to IFNβ was not significantly different for cases and controls (OR 1.28; 95% CI 0.87 to 1.88). There was a non-significant trend towards an increased risk of IFNβ exposure in the breast cancer cases (OR 1.77; 95% CI 0.92 to 3.42), but no evidence of a dose-response effect. Tumour size was similar between IFNβ treated and untreated cases.
CONCLUSIONS: There was no evidence of an increased cancer risk with exposure to IFNβ over a 12-year observation period. However, the trend towards an association between IFNβ and breast cancer should be investigated further.
Source: J Neurol Neurosurg Psychiatry. 2014 Mar. doi: 10.1136/jnnp-2013-307238. (19/03/14)
The University of Virginia (UVa) Medical Center has joined 27 other hospitals around the country in conducting a series of neurological clinical trials. Specifically, UVa recently enrolled in NeuroNEXT (Network for Excellence in Neuroscience Clinical Trials), which is sponsored by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.
UVa is currently recruiting participants for its Phase 2 Clinical Trial to evaluate the safety, tolerability, and activity of ibudilast in patients with primary- or secondary-progressive multiple sclerosis; they hope to recruit 250 male and female subjects ages 21 to 65 years old who have no prior treatment with long-term multiple sclerosis disease modifying therapy or who are receiving glatiramer acetate or interferon beta treatment. Ibudiblast will be administered in conjuction with glatiramer or interferon beta treatment and compared to a placebo.
Participants will receive placebo or 100 mg/day ibudilast for 96 weeks. Primary outcome measures include brain atrophy over 96 weeks and treatment-emergent adverse events over 36 months. Secondary outcome measures include inflammatory, disability, and quality of life statuses, as well as cognitive impairment and neuropathic pain. The study is projected to end in March 2017 with a primary completion date in December 2016.
Ibudilast is special because it is designed to treat patients with progressive multiple sclerosis, and according to Dr. Myla D. Goldman at UVa’s James Q. Miller Multiple Sclerosis Clinic, current medications have failed to stop or slow progressive multiple sclerosis. Consequently, patients have little relief of their symptoms that gradually worsen over time.
Source: BioNews Texas (19/03/14)
As well as lowering cholesterol and cutting stroke risk, statins may slow the progression of advanced multiple sclerosis.
Globally, 2.5 million people have MS. Of these, two-thirds will develop the advanced form of the disease within 15 years of diagnosis. Although several treatments exist for the early phase of the disease – called relapsing-remitting MS – there is no treatment for the more advanced phase, called secondary progressive MS (SPMS).
A team led by Jeremy Chataway of University College London randomly assigned 140 people with SPMS either a daily dose of statins or a placebo for two years. They found that those taking the drug experienced 43 per cent less brain shrinkage – a marker of disease progression – per year compared with those taking a placebo. Statin recipients also deteriorated more slowly than placebo recipients as measured by two scales of disability.
Because of the short length of the trial, the researchers had expected to see a 20 to 30 per cent slowing in brain shrinkage at best, and did not expect to see any improvements in disability score because symptoms change so gradually. "The primary outcome was the [brain] atrophy rate, so any improvement in quality of life was a bonus," says Chataway. "It was unexpected, and the icing on the cake given the small scale of the study."
All the difference
The differences in the disability scores were modest but would have made a difference to the research participants. One measure, rated by doctors, ran from zero to 10, with zero being perfectly healthy. Both groups began the trial with average scores of about 5.8. After the trial, the average score for statin recipients was 5.93, compared with 6.35 for those on placebo. "It doesn't sound much, but going from 6 to 6.5 can mean moving from reliance on one walking stick to two, while scoring 7.0 can mean confinement to a wheelchair," says Chataway.
A second scale, run from 29 to 116 (most severe) and rated by research participants, echoed the improvements noticed by doctors. Those on statins, averaged 70.1 after two years, compared with 76.1 for those on placebo, from baseline scores of 70. All the ratings were done "blind", to avoid bias.
Chataway now hopes to mount a larger, three-year trial in up to 900 people with MS to confirm that the improvements in disability were down to the statin and not mere chance.
Journal reference: The Lancet, DOI: 10.1016/S0140-6736(13)62242-4
Source: New Scientist © Copyright Reed Business Information Ltd 2014 (19/03/14)
The hidden symptoms of Multiple Sclerosis (MS) have been creatively captured in a collaborative effort from Grey Melbourne, Limehouse creative, Infinity Squared and some talented Australian photographers.
Each photographic representation in the Seeing MS campaign depicts a symptom of MS as experienced by someone living with the condition. The challenge of this task was capturing the arbitrary nature of these invisible symptoms, including blurred vision, chronic pain and inescapable fatigue.
The Seeing MS campaign aims to change the public perception of the disease in Australia and promote a deeper understanding.
Executive Creative Director at Grey Melbourne, Michael Knox, said " …we hope we've created something that pushes multiple sclerosis and it's hideous symptoms into the limelight. Something that starts a new conversation and takes us closer to understanding MS."
The haunting photographs will be used in an outdoor campaign and the personal account of each story/symptom as a television commercial.
The project also resulted in the creation of nine photographic filters that mimic the symptoms of the disease. These are available on a Seeing MS App.
Source: B & T Copyright © 2014 Cirrus Media (18/03/14)
Dysport® study positive in the treatment of patients with neurogenic detrusor overactivity(18/03/14)
Ipsen announces positive results from phase IIa clinical study of Dysport® in the treatment of patients with Neurogenic Detrusor Overactivity (NDO).
Results show significant decrease in urinary incontinence episodes and improvement in patient quality of life.
Ipsen today announced positive results from its phase IIa clinical trial assessing Dysport® in the treatment of Neurogenic Detrusor Overactivity (NDO) in patients with urinary incontinence not adequately managed by anticholinergics.
Results show that treatment with Dysport® was associated with a mean reduction from baseline of urinary incontinence episodes greater than 75%, 12 weeks after the injection, regardless of how the drug is administered. These results were achieved with a single dose of Dysport® 750 Units injected in either 15 or 30 sites in the detrusor muscle. Efficacy was confirmed by improvement in urodynamic parameters and quality of life. The safety profile observed in the study is consistent with the safety profile expected in this indication.
Claude Bertrand, Executive Vice-President R&D, Chief Scientific Officer of Ipsen said: “These results are very encouraging for the Dysport® franchise, which has the opportunity of potentially expanding into urology, a core therapeutic area for Ipsen”. Claude Bertrand added: “We are excited about the potential benefits Dysport® could bring to patients suffering from NDO”.
Dysport® is an injectable form of botulinum toxin type A (BTX-A), which is isolated and purified from Clostridium BTX-A bacteria. It is formulated as a complex of BTX-A with haemagglutinin, a large therapeutically inert protein used to stabilise the toxin. Dysport® is formulated with lactose (Ph Eur/NF) and human serum albumin (Ph Eur/USP) and is supplied as a lyophilised powder.
Dysport® was first registered for the treatment of blepharospasm and hemifacial spasm in the United Kingdom (UK) in 1990, and is licensed in more than 75 countries for various indications including: blepharospasm, adult upper and lower limb spasticity, hemifacial spasm, spasmodic torticollis (ST) (previously referred to as cervical dystonia), paediatric spasticity due to cerebral palsy (CP), axillary hyperhidrosis, and glabellar lines. Dysport® is not currently approved in any country for the treatment of NDO.
About Neurogenic Detrusor Overactivity (NDO)
NDO is a chronic condition defined by abnormal bladder contractions related to an underlying neurological condition such as multiple sclerosis (MS) or spinal cord injury (SCI). Current standard of care includes self-catheterisation or oral anticholinergic medications that present frequent side-effects and insufficient efficacy on the long term. In case of inadequate treatment response to anticholinergics, a botulinum toxin-A is indicated, before considering rescue treatments such as neuromodulation or bladder augmentation surgery in refractory cases.
About the phase IIa clinical trial
This phase IIa, multinational, randomised, placebo-controlled study aimed to investigate the efficacy and safety of one cycle of a single dose of 750 U Dysport® in 47 patients with NDO secondary to Multiple Sclerosis (MS) or Spinal Cord Injury (SCI). Follow-up duration was of 96 days. The primary endpoint was the mean change from baseline in daily urinary incontinence episodes frequency 12 weeks after the injection for each administration mode, i. e. 15 or 30 injections points at a constant volume by injection site. Secondary endpoints included other clinical endpoints, urodynamic measurements, and safety.
Source: EIN Newsdesk © Thomson Reuters 2014 (18/03/14)
Scientists have reported that they have created at least five new experimental substances - based on a tiny protein found in cone snail venom - that could someday lead to the development of safe and effective oral medications for treatment of chronic nerve pain. They say the substances could potentially be stronger than morphine, with fewer side effects and lower risk of abuse.
"This is an important incremental step that could serve as the blueprint for the development of a whole new class of drugs capable of relieving one of the most severe forms of chronic pain that is currently very difficult to treat," said David Craik, Ph.D., who led the study.
His presentation is one of more than 10,000 scheduled to occur at the 247th National Meeting & Exposition of the American Chemical Society (ACS), the world's largest scientific society, taking place here through Thursday.
Craik, who is at the University of Queensland, explained that acute pain occurs when the nervous system is stimulated by a wound or injury and naturally subsides over time. In contrast, chronic neuropathic pain kicks in when the nervous system itself is damaged. This type of pain - which is often triggered by diabetes, multiple sclerosis and other diseases - can last for months, years or even decades. Current treatments for chronic neuropathic pain have serious side effects and provide relief to only about one in every three patients, he said.
One possible solution that Craik and his colleagues are investigating comes from an unlikely source, the cone snail. Cone snails are marine animals that use venom to paralyze their prey. This venom contains hundreds of peptides (small proteins) known as conotoxins. But in humans, Craik says some of these conotoxins appear to have analgesic effects. So far, however, only one conotoxin-derived medication has been approved for human use. This drug, ziconotide, has one big drawback: It has to be infused directly into the lower part of the spinal cord - a clearly invasive procedure.
The team is working to develop a conotoxin-based drug that can be taken orally, which would be much more practical for patients. In previous research, they found a way to modify conotoxin peptides so they formed circular chains of amino acids. As a result, the modified peptides - which are essentially tied into a loop - are extremely stable and resistant to enzymes in the body.
In laboratory rats, a common stand-in for humans in many experiments, a single, small oral dose of a prototype drug based on one of these looped conotoxins appeared to significantly reduce pain, as measured by a standard protocol. Based on this research, the scientists concluded that this prototype drug was about 100 times more potent than morphine or gabapentin, the two drugs that are considered the "gold standard" treatments for chronic nerve pain.
Addiction is less of a concern, Craik said, because conotoxins act on different receptors in the brain than morphine and other opiate drugs.
"We don't know about side effects yet, as it hasn't been tested in humans. But we think it would be safe," Craik said. "It acts by a completely different mechanism than morphine so we think it has a minimal possibility of producing the side effects of that medication. That is one of the big advantages of this drug."
Craik's team also has developed at least five additional new substances based on the looped conotoxin prototype drug. They are currently evaluating the therapeutic potential of these new substances, which they developed by tweaking the composition of the amino acids in the prototype conotoxin drug used in their initial animal studies. They are also seeking funding and approval for human studies. Craik says it will likely be at least two years before such studies begin.
Source: Medical News Today © MediLexicon International Limited 2004-2014 (17/03/14)
On 12 March, Ain Shams University — one of the two oldest and most established universities in Cairo — witnessed the opening of a first-of-its-kind unit for treating Multiple Sclerosis in Egypt.
The event, attended by a big number of experts in the field, was another opportunity to tackle the little talked of agony of MS sufferers, their statistical number, and the challenges they face.
Multiple Sclerosis, or MS, is a disease whose reasons are still shrouded in mystery. With MS, the autoimmune system attacks its own tissues, eventually destroying a fatty substance that protects nerve fibres in the brain and the spinal cord.
In Egypt, the most recent statistics by the Ministry of Health show that MS cases comprise 1.4 percent of all neurological diseases, and that the number of sufferers in the country is approximately 50,000.
The major problem with MS is that it usually strikes at a very early age, affecting those between the ages of 20 and 40 in 70 percent of cases.
“Imagine a young man or woman, as young as 20 years old, struck by an immunity disease and facing the possibility of an inability to talk, walk and live normally within a few years. That is the tragedy of MS, if left untreated,” Dr Osama Abdel Ghany, professor of neurology Ain Shams University, told Ahram Online.
Dr Abdel Ghany described the inauguration of the unit as an opportunity to draw attention to the disease that lays a high burden on society, explaining that although the percentage of sufferers is not large, most sufferers are young, and almost 40 percent of them end up with complete disability if left untreated, thus depriving them and society of their productive lives.
Dr Abdel Ghany also drew attention to the fact that more awareness is needed regarding the financial toll of the disease. “Egyptian medical insurance only provides an allowance of 2,000 LE per month to the patient, which covers a tiny amount of the expenses, which range annually from 70,000 to 140,000 LE per person,“ he told Ahram Online.
“That’s why the inauguration of this unit is a big step,“ said Dr Hany Aref, professor of neurology. He explained that MS is a challenge from the beginning, because its symptoms, which commonly start with visual and sensory fluctuations, go sometimes unnoticed and are often mistaken for other causes.
Dr Samia Ashour, head of the Psychiatry and Neurology Department, takes heart in the strides Ain Shams University is taking to upgrade its MS service level and research facilities, thanking Novartis company for their cooperation and stating that two months ago a new stroke centre had been inaugurated, and that the new MS unit comes as the latest accomplishment in addressing serious risks to health.
The service capacity offered by the new facility was described by Dr Magd Zakria. "Around 60 to 80 patients will benefit every month to ensure that top quality service is maintained. More patients will receive related services." He added that the unit is equipped with follow-up devices, an ECG monitor and offers a daycare facility.
The inauguration panel also mentioned that although the causes of MS are still shrouded in mystery, and in spite of the fact that there is no known cure until now, the course of the disease can be much modified and the symptoms managed to a great extent if the right treatment is given — particularly with the use of fingolimod - an oral medication approved by the US Food and Drug Agency in 2010.
In addition to constant medical monitoring and taking medication prescribed by doctors, lifestyle changes that a MS patient needs to take into consideration include:
· Good nutrition that includes rich sunflower oil, vegetables and fruits, and minimising saturated fats.
· A good intake of vitamin D.
· Limited exposure to heat. Even showers should not be with hot water.
· Avoiding varied kinds of stress.
· Maintaining peace of mind and steering away from exhaustion.
According to statistics provided by the WHO, for every 100,000 persons, 30 are affected by the disease, with a total number reaching up to 2.5 percent worldwide. It is noted also that women are twice as likely to develop MS. After road accidents, MS is regarded as the second most common cause of disability around the world.
Source: Ahram © 2014 Ahram Online (17/03/14)
Therapy optimisation in MS: a prospective observational study of therapy compliance and outcomes(14/03/14)
Data sources for MS research are numerous but rarely provide an objective measure of drug therapy compliance coupled with patient-reported health outcomes. The objective of this paper is to describe the methods and baseline characteristics of the Therapy Optimisation in MS (TOP MS) study designed to investigate the relationship between disease-modifying therapy compliance and health outcomes.
Methods: TOP MS was designed as a prospective, observational, nationwide patient-focused study using an internet portal for data entry.
The protocol was reviewed and approved by Sterling IRB. The study was registered with ClinicalTrials.gov.
It captured structured survey data monthly from MS patients recruited by specialty pharmacies. Data collection included the clinical characteristics of MS such as MS relapses.
Disability, quality of life and work productivity and activity impairment were assessed quarterly with well-validated scales. When events like severe fatigue or new or worsening depression were reported, feedback was provided to treating physicians.
The therapy compliance measure was derived from pharmacy drug shipment records uploaded to the study database. The data presented in this paper use descriptive statistics.
Results: The TOP MS Study enrolled 2966 participants receiving their disease-modifying therapy (DMT) from specialty pharmacies.
The mean age of the sample was 49 years, 80.4% were female, 89.9% were Caucasian and 55.7% were employed full or part time. Mean time since first symptoms was 11.5 years; mean duration since diagnosis was 9.5 years.
Patient-reported EDSS was 3.5; 72.2% had a relapsing-remitting disease course. The most commonly reported symptoms at the time of enrollment were fatigue (74.7%), impaired coordination or balance (61.8%) and numbness and tingling (61.2%).
Half of the sample was using glatiramer acetate and half was using beta-interferons.
Conclusion: Demographic and clinical characteristics of the TOP MS sample at enrollment are consistent with other community-based MS samples, and the sample appears to be representative of DMT users in the US. TOP MS data can be used to explore the associations between disease-modifying therapy compliance and health outcomes.Trial registration: ClinicalTrials.gov (NCT00819000).
Author: Patricia K CoyleBruce A CohenThomas LeistClyde MarkowitzMerriKay Oleen-BurkeyMarc SchwartzMark J TullmanHoward Zwibel
Credits/Source: BMC Neurology 2014, 14:49
Source: 7thSpace Interactive © 2014 7thSpace Interactive (14/03/14)>
A new study shows that relapsing-remitting MS patients who suffer from fatigue may also be running a fever.
The fatigue multiple sclerosis (MS) patients experience is very different from the type experienced by healthy people. According to the National Multiple Sclerosis Society, fatigue occurs in about 80 percent of MS patients and “can significantly interfere with a person's ability to function at home and work." Fatigue is often cause for early retirement.
“When I share my research on fatigue in MS with colleagues or friends,” Victoria M. Leavitt, Ph.D., a neuropsychologist and co-founder of the Manhattan Memory Center in New York City told Healthline, “they say they know what it’s like, but the truth is they don’t.”
MS fatigue usually occurs every day, with lack of energy peaking by mid-afternoon. Onset can be sudden and is aggravated by heat.
In her earlier work, Leavitt found that outdoor temperature has an impact on cognition in MS patients. The results of that study made the team question whether internal temperature might also play a role in the disease process.
In their new study, Leavitt along with James F. Sumowski, Ph.D., a senior research scientist in neuropsychology and neuroscience at the Kessler Foundation, found that patients with relapsing MS who complained of fatigue also had a low-grade fever.
They studied 50 patients with relapsing-remitting MS (RRMS), 40 healthy controls, and 22 patients with secondary-progressive MS (SPMS). They discovered that warmer body temperatures in patients with RRMS were linked to more extreme fatigue. The volunteers with SPMS did not have a fever. This is the first-ever demonstration that body temperature is elevated in those with RRMS, and that it directly impacts their level of fatigue.
Healthline asked Leavitt and Sumowski for more details about their findings.
What's Causing the Low-Grade Fever?
"We think it is a disease-related inflammatory processes," explained Sumowski, “We know that elevated body temperature is linked to inflammation when otherwise healthy people experience a fever, as well as in other diseases (i.e., temperature of the joints in people with rheumatoid arthritis, temperature of the brain in acute stroke patients).”
“Rather than chronic inflammation, however, we think that body temperature may fluctuate with day-to-day fluctuations in inflammation among RRMS patients, although this still needs to be investigated directly," he added. "Indeed, many RRMS patients report day-to-day fluctuations in fatigue.”
Why Not Secondary-Progressive MS?
“This is a great question,” said Leavitt, “and it relates to our hypothesis that body temperature is related to inflammation. We know that RRMS is associated with inflammatory processes, which can lead to [relapses]. In contrast, inflammatory processes are less pronounced in progressive forms of the disease.”
“Indeed, there is a shift away from inflammatory lesions and clinical exacerbations after persons convert from RRMS to secondary-progressive MS (SPMS)," she added. "It makes sense, therefore, that (if body temperature is related to inflammation) body temperature would be higher in RRMS relative to SPMS.”
Is Heat Slowing Down Brain Signals?
Just as electronic devices malfunction when they become overheated, a fever might interfere with signals from the brain to the rest of the body. But according to Leavitt, there is surprisingly little to document this.
“For us, it is unclear whether body temperature has a direct relationship on neural transmission, or whether, alternatively, inflammation slows neural transmission and elevates body temperature," she said. "This is an important question for future research.”
During their study, Leavitt and Sumowski made an unexpected observation: hospital grade oral thermometers were surprisingly inaccurate. “Once we switched to in-ear thermometers,” said Leavitt, “we got much more accurate results.”
They theorized that if measuring body temperature from within the ear is more accurate, and the point of contact is closer to the brain itself, perhaps the fever is emanating from the disease activity within the brain. Leavitt referred to a study published last year that found that people with RRMS who had an elevated brain temperature experienced a greater level of disability.
“We are interested in extending this work,” said Leavitt, “as we think that brain temperature may bring us even closer to the source of elevated temperature and help us to understand whether it is related to inflammatory processes, fatigue, and other clinical symptoms.”
If you have RRMS and suffer from daily fatigue, what can you do? Besides the obvious goal of keeping your body cool, Sumowski said people with MS might want to, “avoid situations may cause additional inflammation, including smoking, obesity, and exposure to allergens.”
Source: Healthline Copyright © 2005 - 2014 Healthline Networks, Inc (13/03/14)
Multiple sclerosis (MS) can be devastating to younger individuals given that it usually strikes during the peak productive ages of 20 to 50 years. When patients with MS are confronted with this potentially debilitating condition and the recognition that no cure for MS currently exists, their quality of life (QOL) can suffer.
Recent research indicates that patients with MS report QOL that falls more than 1 standard deviation below that of the general population (mean health state score 59.7 ± 22.4 for patients with MS versus 82.5 for the general population).1 In this registry study of 4516 patients with MS, health-related QOL ranked poorly, particularly in men, older individuals, people with a long duration of MS, and those with a progressive form of the disease. Among the total cohort of MS patients, about 83% reported difficulties with usual activities, 76% indicated problems with pain or discomfort, 76% struggled with mobility, and 58% reported problems with anxiety or depression.
Although disease-modifying therapies hold promise for reducing MS symptoms, preventing relapse, and delaying disease progression, many of these agents produce little improvement in QOL.2,3 This suggests that either better disease-modifying therapies or adjunctive treatments may be needed to improve specific MS symptoms in order to positively influence QOL.
Two comorbid conditions that are particularly relevant in individuals with MS and which are amenable to symptomatic treatment are pain and depression. “Researchers from our team and others in the field have consistently noted a strong association between depression and pain severity, but elements of the pain-depression relationship haven’t been fully researched, particularly in individuals with MS,” said Kevin Alschuler, PhD, acting assistant professor in the Department of Rehabilitation Medicine at the University of Washington School of Medicine in Seattle.
To better address this issue, Dr. Alschuler and colleagues surveyed 161 individuals with MS to evaluate the prevalence of pain and depression using a variety of methods for defining these conditions.4 The findings were striking: “As many as 1 in 5 patients with MS experience both pain and clinically significant depression, and 42% to 78% of patients with MS experience pain, depression, or both,” Dr. Alschuler noted.
The results not only reinforce the importance of considering both pain and depression in patients with MS, they also lend insight into the pattern of these comorbidities. For example, “When depression was present, pain was highly likely to also be present. Relatively few patients in our sample had depression without also having pain,” said Dr. Alschuler, who also found that patients with comorbid depression visited medical providers more frequently for pain relief and used a greater number of pain treatments than patients without comorbid depression.5
Recognizing that a large treatment gap in QOL exists for patients with MS is half the battle; the other half is taking proactive measures to address the situation. Dr. Alschuler believes that, in addition to managing symptoms and delaying disability progression, assessing and promoting patient QOL should be a primary goal of MS treatment.
“We’re very interested in having our research impact clinical practice and, in fact, believe that it has already helped us take our first steps in that direction,” said Dr. Alschuler, whose research team recently received grant funding for a study that seeks to improve the model of care for depression and pain in patients with MS.
This new study will aim to compare the delivery of standard care versus collaborative care to 200 outpatients with MS who have depression, chronic pain, or both. Under the collaborative care approach, a care manager—that is, a nurse supervised by expert physicians, psychiatrists, and psychologists—will coordinate and provide evidence-based therapy for depression and pain that matches the patient’s goals and preferences. Although this strategy has proven successful across a variety of ailments, it has never been evaluated in patients with comorbid MS, pain, and depression.
“We’re particularly excited about the specific care model we’re testing, as we believe that it would be feasible for the model to be implemented in standard clinical practice if our study supports its use,” said Dr. Alschuler.
By Kara Nyberg, PhD
Jones KH, Ford DV, Jones PA, et al. How people with multiple sclerosis rate their quality of life: an EQ-5D survey via the UK MS Register. PLoS One. 2013;8:e65640. Abolfazli R, Hosseini A, Gholami Kh, et al. Quality of life assessment in patients with multiple sclerosis receiving interferon beta-1a: a comparative longitudinal study of Avonex and its biosimilar CinnoVex. ISRN Neurol. 2012;2012:786526.
Berger JR. Functional improvement and symptom management in multiple sclerosis: clinical efficacy of current therapies. Am J Manag Care. 2011;17(suppl 5):S146-S153. Alschuler KN, Ehde DM, Jensen MP. The co-occurrence of pain and depression in adults with multiple sclerosis. Rehabil Psychol. 2013;58:217-221. Alschuler KN, Jensen MP, Ehde DM. The association of depression with pain-related treatment utilization in patients with multiple sclerosis. Pain Med. 2012;13:1648-1657.
Source: MedPage Today © 2014 Everyday Health Media, LLC (12/03/14)
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)