MS news and research
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Patients with multiple sclerosis are more than twice as likely as the general population to attempt suicide and almost twice as likely to actually complete suicide, a new study has claimed.
The study also had some interesting results with regard to education. Although highly educated patients with MS are less likely to attempt suicide than their counterparts without MS, this is not the case when it comes to completed suicide.
Patients with MS should be screened for psychiatric disorders, said lead researcher Philip Brenner, MD, PhD student, Department of Neuroscience, and resident psychiatrist, Karolinska University Hospital, Stockholm, Sweden.
"Since neurologists are primarily the ones treating MS patients, they should be aware of the increased suicide risk and the risk for suicide attempts among these patients," Dr Brenner told Medscape Medical News.
"It's very important to include screening measures for mental health in clinical practice."
As well as depression, which is probably the most important risk mediator for suicide prevention in MS, physicians might also watch for personality changes, for example, having less impulse control and increased substance abuse, he said.
He presented their results at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015.
The study included 29,617 patients with MS from the combined Swedish National Patient Register and Swedish MS Register. It also included 10 controls without MS for each case from the Swedish general population who were matched with the MS group for year of birth, sex, and county of residence.
Researchers used diagnostic codes for intentional self-poisoning or injury to identify attempted suicides, and the Swedish Cause of Death register to identify completed suicides. They excluded deaths in which the intent was unclear.
There were 423 attempted suicides among patients with MS during the follow-up period (1968 to 2012) for an incident rate (IR) of 116.5 per 100,000 person-years. In patients without MS, the IR was 50.8. The adjusted hazard ratio (HR) was 2.18.
Women were at 30 per cent higher risk for attempted suicide compared with men in both the MS and control groups.
From census data, the researchers determined categories of education level achieved by study participants. As expected, they found that the risk for attempted suicide was lowest among patients with MS and controls with the highest level of education (14 or more years).
During the follow-up period, 114 patients with MS who committed suicide, for an IR of 30.31 per 100,000 person-years. This compared to an IR in patients without MS of 16.8. The adjusted HR for completed suicide was 1.87.
Dr Brenner said patients with MS who committed suicide chose means that were less violent than those without MS — for example, taking an overdose of pills rather than other means. "We don't have a good explanation for this," he said.
The risk for completed suicide was not lower among highly educated patients with MS, although it was for educated controls. There's evidence that an adverse event in adulthood (such as an MS diagnosis) can counteract the protective effect of socioeconomic status in terms of depression rates. "Maybe that's also true for MS," said Dr Brenner.
"With this difference in mind, it's possible that the effect of education is different in the two groups," he said. "But this needs to be investigated further."
Source: Medscape Medical News © 2015 WebMD, LLC (09/10/15)
The possible protective effect of pregnancy on multiple sclerosis activity in women does not extend to patients who stop taking Tysabri after conceiving, researchers revealed at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Of 59 women treated with Tysabri who discontinued the drug during pregnancy, 12 experienced relapses and seven others had two or more relapses for a relapse rate of 32.2 per cent, reported Emilio Portaccio, MD, a neurologist at the University of Florence.
“In our sample, following Tysabri suspension, pregnancy did not prevent disease reactivation,” he said in his oral presentation.
In addition, he reported the rate of spontaneous abortions among women who had been taking Tysabri was greater than it was for a similar cohort of women taking interferon therapies or who had no treatment with disease-modifying drugs.
The study included MS patients who had been diagnosed and treated with Tysabri at one of 21 Italian centres from 2010 to 2013. The women were followed for at least 12 months after delivery. The researchers compared outcomes for women on Tysabri who had discontinued therapy — either to have a baby or who became pregnant — with women with MS who had been treated with interferon agents and women who were not exposed to disease-modifying drugs, or who had discontinued interferon therapy at least four weeks before conception. They were also compared to the general Italian population.
Of the 75 women who stopped their Tysabri therapy, there were 59 pregnancies, 45 live births, and 11 spontaneous abortions at a rate of 18.7 percent. The researchers compared outcomes for that group with those of 398 women taking interferon-based treatments, in which there were 88 pregnancies, 75 live births, and seven spontaneous abortions at a rate of 8 percent, a statistically significant difference. Of the women not exposed to disease-modifying drugs, there were 295 live births, 20 spontaneous abortions at a rate of 6.6 per cent, one stillbirth, and two extra-uterine pregnancies.
Dr. Portaccio said that all of the groups fell within the general population in Italy, however, where the spontaneous abortion rate declined between 4.4 per cent and 21.6 per cent.
In the Tysabri-exposed pregnancies, there was a slight reduction in the baby birth rate, but that was comparable to what was seen in the women whose babies were exposed to interferon in the womb. “We observed no major birth defects and no difference between the groups in the rate of birth defects,” he said.
Commenting on the study, the session co-moderator Charlotte Teunissen, PhD, an associate professor of medicine and head of neurochemistry at the VU University Medical Center of Amsterdam, told the Neurology Today Conference Reporter that the study suggests that “patients and doctors [should] wait as long as possible before taking women off natalizumab when they become pregnant.”
She added: “Pregnancy normally has a very positive effect on multiple sclerosis activity, but this study shows that this effect is too small to overcome the very strong rebound observed with discontinuation of Tysabri.
“Doctors should be encouraged to hold off suspending Tysabri unless they fear continuing would harm the fetus,” Dr. Teunissen said. “This would obviously be up to the discretion of the treating physician and the patient. The greatest risk would be spontaneous abortion, although it was within the normal range in this study. There did not seem to be any greater risk of birth defects or even low birthweight.”
Source: Neurology Today Copyright © 2015 American Academy of Neurology (09/10/15)
Preliminary findings from an ongoing study of multiple sclerosis patients suggest the dosing interval for Tysabri can be as much as doubled from the label-recommended standard without sacrificing efficacy, and with potentially less risk of progressive multifocal leukoencephalopathy (PML) -- even among patients with more than average PML risk, researchers claim.
Among some 2,000 patients -- about half of whom were receiving Tysabri at intervals ranging from 31 to 61 days, versus the standard 28-day cycle in the other half -- measures of efficacy were the same or better in those on extended-interval dosing, said Lana Zhovtis-Ryerson, MD, of NYU Langone Medical Centre in New York City, who presented the findings at a platform session during the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.
Furthermore, no cases of PML were seen in the extended-dosing patients, compared with four among those taking Tysabri on the conventional four-week schedule, she said.
She cautioned, however, that the findings on PML risk are not yet definitive because there are not yet enough data in the ongoing study for the differences to reach statistical significance.
But at this point, it does appear that the extended-dosing strategy does maintain efficacy in relapsing-remitting MS patients.
Earlier this year, when Zhovtis-Ryerson and colleagues reported initial results from the study, there were two cases of PML in the standard-dose group versus none receiving extended dosing, and relapse rates and MRI activity levels were similar. At that time, and again here, she said 1,248 patient-years of exposure would be needed to pronounce a significant advantage for one dosing strategy.
Currently, she said the standard-dose group had 1,052 patient-years among JC virus-positive participants and 1,090 patient-years in the extended-dosing group.
However, accrual of patient-years of exposure is proceeding slowly, she told MedPage Today, and the research team expects it will be another 18 months before both groups reach the 1,248 mark.
Label instructions for Tysabri dosing call for the drug to be given every four weeks. But researchers have wanted to determine whether the same degree of clinical efficacy, in reducing risk of relapses and MRI lesion activity, can be maintained with longer intervals -- the point being to reduce the overall drug exposure and with it, presumably, the risk of developing PML.
Rates of PML have been found to increase with years of Tysabri exposure, but it remains unknown whether reducing the exposure in terms of milligrams per year will also cut the PML risk.
PML has been the biggest barrier to use of Tysabri, which otherwise is a highly effective and relatively safe agent for relapsing-remitting MS. Among patients positive for JC virus (the actual causative agent) who remain on Tysabri for more than two years at standard dosing, between 0.5 and one per cent will develop PML, depending on prior exposure to immunosuppressants. Roughly 20 per cent of PML cases are fatal and many survivors have permanent disabilities.
The current study's design involves regular chart reviews, conducted on a prospective basis but without randomized treatment assignments, of patients receiving natalizumab on a variety of dosing schedules chosen by their treating physicians on an individualized basis. Zhovtis-Ryerson and colleagues have stratified patients into the following groups:
Standard dosing (every four weeks)
Extended dosing (every 31 to 61 days)
That no patients in the latter group developed PML, versus four with standard dosing, is all the more impressive because the recognized risk factors for PML were more common in those receiving the extended dosing -- as might be expected since clinicians may be inclined to recommend less frequent natalizumab dosing for patients deemed to have high PML risk.
Zhovtis-Ryerson emphasized that data from the current study may never be fully adequate to justify extended dosing as a routine strategy. She urged that a prospective, randomised non-inferiority trial be conducted.
Source: MedPage Today © 2015 MedPage Today, LLC (09/10/15)
Multiple sclerosis patients taking the cannabis-based spray Sativex to relieve spasticity are getting approximately the same degree of benefit expected from the product's formal trials, according to interim results from two observational studies from Italy reported here.
Modest but statistically significant improvement in spasticity scores (10-point Numerical Rating Scale, NRS) has been seen among 322 patients who added Sativex to standard anti-spasticity drugs and/or physical therapy, according to a group led by Maria Trojano, MD, of the University of Bari, whose ongoing study is called MOVE 2 and who reported data from the first three months after enrollment.
A separate study dubbed SA.FE led by Francesco Patti, MD, of the University of Catania, has also yielded similar results during the first few months of therapy, with about 40% of 547 patients showing at least a 30% improvement in NRS scores at 6 months.
Both studies were reported at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.
Sativex is a 50:50 mixture of the cannabis components THC and cannabidiol, sprayed into the mouth daily to help control spasticity symptoms. It was approved in Italy for marketing in mid-2013 on the basis of randomized trials showing a benefit over placebo, primarily in patient-reported measures. Those findings led the American Academy of Neurology last year to declare Sativex appeared effective in patients' subjective judgment (though the group questioned the product's efficacy according to objective measures).
Because clinical trials usually enroll carefully selected patients, with many exclusions and close monitoring of those enrolled, there are often questions about the relevance of these results in real-world patients. Hence, the MOVE 2 and SA.FE studies were started to examine how Sativex is working in routine practice environments.
MOVE 2 actually began in Germany and was subsequently extended to other European countries following Sativex's approval there, Trojano and colleagues noted. In the Italian version, outcomes according to both the patient-reported NRS score and the objective Ashworth scale (measuring resistance to muscle stretching) are being collected.
The current report included results from the first 322 patients to complete three scheduled clinic visits after starting Sativex. The initial visit was at enrolment, the second occurred one month later, and the third took place 2 months after that. Patients were asked about concomitant treatments and adverse effects. Data on quality of life, satisfaction with treatment, and other issues are being collected as well, but were not reported here.
More than two-thirds of MOVE 2 participants said they were also taking baclofen, and smatterings of others reported using benzodiazepines, pregabalin, gabapentin, and/or other agents. About half were taking physical therapy as well.
At the one-month visit, 83 per cent of patients had NRS scores that were at least 20 per cent better than at the baseline visit. At the three-month evaluation, with 203 patients having sufficient data, about one-quarter showed at least 30 per cent improvement from baseline in NRS score, and most of the others continued to use Sativex despite showing less than 30 per cent improvement.
By the third visit, 22 per cent had discontinued the product. About 40 per cent of those were for lack of efficacy and an equal proportion cited adverse effects; the remainder had become pregnant or had other reasons to stop the drug.
Mean dose at the one-month visit was 6.1 sprays/day (SD 2.5); at the third visit it was 5.1 sprays/day (SD 2.6).
On the objective Ashworth scale, Sativex also appeared effective: from a baseline mean of 2.6 on the 4-point scale, the mean declined to 2.2 at the second visit (P<0.0001) and stood at 2.3 at the third visit (P<0.0001 versus baseline), with 220 and 149 patients evaluated at the respective visits.
More than 80 per cent of patients reported no adverse effects; of those that did, the chief complaints were dizziness, confusion, nausea, and somnolence.
Trojano and colleagues indicated that they expect final results next year.
For the SA.FE study, Patti and colleagues indicated that their data were not much more mature, with only about one-third of the 1,534 patients currently enrolled having reached the six-month mark. Also, their report only had NRS data.
However, those results clearly support a benefit for Sativex during this time frame. In the first month, there was an average 22.6% decrease in NRS score among all participants, with 62% of patients obtaining at least 20% improvement.
About 600 patients have discontinued thus far -- as in MOVE 2, the most common reasons were lack of efficacy and adverse effects.
Source: MedPage Today © 2015 MedPage Today, LLC (09/10/15)
Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF) is effective at lowering disease activity long-term in patients with relapsing-remitting multiple sclerosis (RRMS), according to Eva Havrdova, MD, of Charles University of Prague.
The findings were being presented in a poster session at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2015) in Barcelona, Spain.
A duo of studies, DEFINE and CONFIRM, previously found patients taking DMF were nearly two times as likely to show no disease activity (NEDA). The findings proved to hold true for five years and the research moved onto an eight-year extension study, ENDORSE. Long-term results, however, were lacking.
Havrdova and team randomised patients to receive either DMF 240 mg twice per day, three times per day, a placebo, or glatiramer acetate. Overall NEDA was defined as patients with no relapses, no 12-week Expanded Disability Status Scale (EDSS)-confirmed progression, no gadolinium-enhanced lesions, and no new or enlarged T2 lesions.
After two years, 1,118 out of 1,736 ENDORSE patients had clinical NEDA and only 618 did not. Magnetic resonance imaging (MRI) results showed that out of the 799 patients who had data on all four components of NEDA, 171 had overall NEDA and 628 did not.
“At Year three in ENDORSE, the annualised relapse rate was significantly lower in patients with clinical and overall NEDA vs those without,” the authors confirmed.
“Throughout the three years in ENDORSE, clinical and overall NEDA patients maintained significantly lower EDSS scores than those without.”
The outcomes suggest that compared to a placebo, DMF significantly reduces disease activity.
Source: MD All Specialities Copyright MD Magazine 2006-2015 Intellisphere, LLC (09/10/15)
A fully-automated and interactive online fatigue management program for patients with multiple sclerosis is comparable to in-person cognitive behavioural therapy (CBT) for the reduction of fatigue, according to data presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Barcelona.
In previous trials, face-to-face CBT or exercise programs were shown to be efficacious in reducing fatigue in patients with MS. For this study, Jana Poettgen, a cognitive psychologist at the University Medical Centre Hamburg Eppendorf in Hamburg, Germany, and colleagues developed the ELEVIDA online fatigue management program based on a manualised face-to-face CBT intervention.
The researchers sought to see how the intervention primarily affected fatigue as measured by the Chalder Fatigue Scale, as well as cognition, quality of life, anxiety, mood, and self-reported neuropsychological function in patients with MS.
The researchers recruited 275 patients from the German Multiple Sclerosis Society; 139 were randomised to ELEVIDA and 136 to the waitlist control group. At baseline, both groups were comparable in age, sex, education, disease duration, and disease course. Overall, 224 of the 275 participants completed an assessment at the three-month follow-up. The ELEVIDA program significantly reduced fatigue, and the ELEVIDA group also reported significant improvements in anxiety and subjective cognitive impairment, however no significant treatment effects were seen for depression or coping.
Overall, the online ELEVIDA program showed efficacy for the reduction of fatigue in MS, and may be a more cost-effective treatment option. The researchers are now studying whether the effects of the program can be maintained over longer follow-up periods.
Reference: Poettgen J et al. Abstract 135. Presented at: The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress; Oct. 7-10, 2015; Barcelona.
Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc.(09/10/15)
Swiss drugmaker Roche has said its experimental treatment for multiple sclerosis performed better in a late-stage clinical trial than a commonly used therapy for the most prevalent form of the condition.
The drug, ocrelizumab, also showed a benefit in primary-progressive MS, or PPMS, giving it the potential to be the first medicine on the market for those patients.
"For decades, we've tried different medicines to treat the primary progressive forms of the disease and nothing has worked," said Dan O'Day, Roche chief operating officer of Pharmaceuticals.
"Ocrelizumab is the first medicine to show an effect in significantly reducing the progression for patients with progressing multiple sclerosis. We're very excited about the benefit that could bring to patients."
The results were from three studies being presented at the European Committee for Treatment and Research in Multiple Sclerosis meeting in Barcelona.
Roche's ocrelizumab is given by infusion once every six months, significantly less frequently than most other MS medicines. The company compared its drug with Merck KGaA's Rebif, an older therapy administered by shot three times a week.
In two studies in relapsing-remitting MS, ocrelizumab reduced patients' risk of flare-ups by almost half over two years compared with Rebif, Roche said in a statement. It also delayed progression of disability by about 40 per cent and reduced brain lesions by about 80 per cent, Roche said.
The most common side effect was infusion-related reactions.
In PPMS, the less common form, Roche compared ocrelizumab with a placebo given the lack of approved therapies. There the medicine also met study goals, reducing the risk of disability progression over 12 weeks by 24 per cent.
The medicine is Roche's first in multiple sclerosis.
Source: CNBC © 2015 CNBC LLC (09/10/15)
Genzyme has announced results from magnetic resonance imaging (MRI) analysis of participants in the Phase III TEMSO clinical trial showing Aubagio was able to slow the loss of brain volume (or atrophy) versus a placebo over two years in patients with relapsing-remitting multiple sclerosis (RRMS).
Brain volume loss (BVL) is widespread in multiple sclerosis (MS), and occurs throughout the disease course at a rate considerably greater than in the general population. In MS, brain volume correlates with and predicts future disability, making BVL a relevant measure of diffuse central nervous system (CNS) damage leading to clinical disease progression, as well as serving as a useful outcome in evaluating MS therapies.
TEMSO MRI data was analysed with SIENA (structural image evaluation using normalization of atrophy). SIENA is a fully automated method for finding temporal brain changes, taking as input two MRI images at different points in time, and giving as output a “change” image, along with a global estimate of percentage brain volume change.
Change in brain volume from baseline was measured in RMS patients who received treatment with Aubagio (14 mg or 7 mg) or a placebo. Results from studies with MS patients treated with Aubagio showed that the incidence of serious adverse events was analogous among patients treated with the drug and those treated with the placebo.
The analysis results will be presented this week, on October 10, at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which is taking place in Barcelona, Spain.
“These results showing the reduction in brain atrophy over two years add to the growing body of data for Aubagio,” said Bill Sibold, Head of Genzyme’s Multiple Sclerosis business. “We remain committed to furthering the understanding of Aubagio and the potential benefits it could deliver to relapsing MS patients.”
Aubagio, a pyrimidine synthesis inhibitor, is an oral compound that inhibits the function of specific immune cells that have been implicated in MS. It is related to leflunomide, a drug used to treat rheumatoid arthritis. Aubagio can inhibit a key enzyme required by white blood cells (lymphocytes) – which in turn reduces the proliferation of T and B immune cells that are active in MS, and also inhibits the production of immune messenger chemicals by T cells.
Aubagio was approved by the U.S. Food and Drug Administration (FDA) in September 2012 for patients with relapsing forms of MS.
“Control or prevention of brain atrophy is an important target for MS treatment,” said Prof. Dr. Ludwig Kappos, Neurology Chair, University Hospital Basel, Switzerland. “This data helps provide further insight into the potential effects in people with RMS.”
Source: Multiple Sclerosis News Today © BioNews Services, LLC 2015 (09/10/15)
Better understanding the relationship between inflammation and biomarkers could help improve treatments for those with multiple sclerosis, according to a new study.
Previous research has found evidence determining that central nervous system (CNS) degeneration depends on inflammation in patients with relapsing-remitting multiple sclerosis (RRMS). Cerebrospinal fluid (CSF) biomarkers appear to reveal if disease modifying therapies (DMT) are reducing disease activity. Lenka Nováková, of the Sahlgrenska University Hospital in Sweden, and colleagues explored the connection further and will explain the findings in a poster session at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2015) in Barcelona, Spain.
The researchers examined 72 patients with RRMS and 39 healthy controls. For the patients with RRMS, 68 were on and four were treatment-native. The data focused on:
. B-cell activity (CXCL13)
. Monocyte/memory T-cell/dendritic cell recruitment (monocyte chemotactic protein 1, MCP1)
. Glial activation (chitinase 3-like 1 or YKL-40)
. Astrogliosis (glial fibrillary acidic protein, GFAP)
. Axonal damage (neurofilament light protein, NFL) in CSF by ELISA
The results showed that compared to the healthy controls, those with RRMS had higher levels of CXCL13, YKL-40, and NFL. In addition, the 47 patients with RRMS who were treated with first line therapies, such as interferon beta, GA, and teriflunomide, had higher levels of CXCL13 and NFL than the 19 patients treated with natalizumab.
“With few exceptions, the interrelation analysis of the biomarkers in RRMS showed significant correlations between inflammatory and degenerative biomarkers. The strongest relationships were found between YKL-40 and GFAP and NFL,” the authors confirmed.
They continued to explain that, “Interestingly, similar and even stronger correlations were found for these biomarkers in [healthy controls].” This suggests that although research continues to support that patients with RRMS have increased YKL-40, which is linked to MS inflammation, it seems that it may also have other roles in healthy individuals.
Source: MD All Specialities Copyright MD Magazine 2006-2015 Intellisphere, LLC. (08/10/15)
Last week, the U.S. Patent Trial and Appeal Board took a long-term Gilenya patent out of commission, putting the Novartis multiple sclerosis drug in line for early generic competition.
While not good news for the Swiss drugmaker, it's not good for rival pharma companies, either as they will also have to contend with copycat versions of Gilenya, the first oral treatment for MS.
"Without novel IP, Gilenya will go generic in 2019 with multiple entrants," Bernstein analyst Ronny Gal said.
Generic Gilenya would join knockoff versions of Teva's MS treatment Copaxone, and together, the two would put pressure on the rest of the treatments for the condition. Though Copaxone is an injectable, it's a mainstay of MS treatment, even in the face of competition from pills like Biogen's Tecfidera and Sanofi's Aubagio, in addition to Gilenya.
With both Gilenya and Copaxone copies available, those rival meds will be in trouble, Gal said.
"By 2019, with both Copaxone and Gilenya generics, I suspect the MS will reasonably lose pricing power and the generics will be used first line," the analyst told FiercePharma.
Source: Fierce Pharma © 2015 FierceMarkets (08/10/15)
New MS drug ‘yields mixed results’(08/10/15)
Multiple sclerosis patients taking a new drug experienced fewer relapse rates but more side effects than patients receiving a standard MS therapy, new research indicates.
In a trial comparing two sets of more than 900 patients with relapsing-remitting multiple sclerosis, scientists found that those taking the drug daclizumab HYP had a 45 per cent lower relapse rate than those taking interferon beta-1a.
But patients on the new drug, which has not yet been approved by the U.S. Food and Drug Administration, saw more side effects. Also, they did not experience significantly slower disease progression than those in the interferon beta-1a group over the first several months.
"This is one more drug for multiple sclerosis, which is of course very welcome, but it's just one in addition to the 11 or 12 drugs we already have," said Dr. Eugene Lai, a neurologist at Houston Methodist Hospital in Houston, who was not involved in the research.
"It does reduce the relapse rate, but it probably doesn't get to the real core of the MS process, and we still don't understand exactly how relapse rate and progression are related," Lai added. "It's still not the definitive treatment for MS yet that can stop it."
The study was published in the New England Journal of Medicine.
In the new study, led by scientists at University Hospital Basel in Switzerland, more than 1,800 patients with relapsing-remitting MS were randomly assigned to receive either daclizumab HYP or interferon beta-1a over a period averaging about two years.
Daclizumab is a so-called monoclonal antibody drug and is thought to work by binding to receptors on immune system cells linked to multiple sclerosis and other autoimmune disorders. Interferon beta-1a is a synthetic version of a natural substance produced in the body that fights infections and other threats.
While daclizumab recipients experienced much lower relapse rates than those on interferon beta-1a, disability progression 12 weeks after the study's start was similar in both groups - 16 per cent with daclizumab and 20 per cent with interferon beta-1a.
But side effects, including serious infections and skin problems such as rash or eczema, were far more common among daclizumab recipients.
Johns Hopkins Hospital in Baltimore was one of the 244 study sites in 28 countries participating in the trial. Dr. Scott Newsome, director of neurology outpatient services at Hopkins, noted that daclizumab might be an easier regimen for MS patients because it's injected under the skin only once every four weeks. Interferon beta-1a requires a weekly infusion.
Another benefit, Newsome said, is that disease progression seemed to be slightly slower at the six-month mark and beyond in daclizumab patients.
"In my mind, that's the outcome measure to look at," he said. "MS is a marathon, not a 50-yard dash. As a group, we need to have better outcome measures in clinical trials that tell us long-term where a patient will be."
Lai and Newsome agreed that FDA approval for daclizumab seems likely, at which point a more complete idea of side effects will be available once the drug hits the market.
Newsome, also an assistant professor of neurology at Hopkins, said he wasn't sure how much daclizumab would cost if it becomes widely available, but it's likely its price would be far higher than for interferon beta-1a, which has been used for many years to treat MS.
"I think it's fantastic that we have a number of therapies to treat MS patients, because certainly throughout the years we're noticing an improvement in patients' overall quality of life and decreased disability over time," he said. "But it's becoming more complicated in terms of which medications we choose first or second, and some of what we decide is not driven by the doctor; often it's driven by the patient and insurer."
If daclizumab is FDA approved for use, Lai and Newsome said physicians should be vigilant for side effects.
"I myself will probably wait and let it be on the market for a while to make sure it's safe before I use it," Lai said. "We're encouraged to have so many effective medications for MS, but it's also kind of confusing to weigh the benefits versus the side effects and risks. It's important for patients to go to a doctor with more expertise in the treatment of MS to get the most benefit and select the right medication for them."
Source: HealthDay Copyright © 2015 HealthDay (08/10/15)
People with multiple sclerosis tend to develop it later if they had regular sun exposure as teenagers, a new study suggests -- adding to evidence linking the condition to a lack of sunlight and vitamin D.
The study found sun exposure during adolescence seemed to influence the age at which people developed MS: The more summer sun they soaked up, the later their symptoms appeared.
Of nearly 1,200 Danish adults with MS, those who'd spent time in the sun every summer day developed symptoms two years later, on average, versus people who'd gotten less sun.
The findings do not mean that basking in the sun will prevent or treat MS, experts stressed.
But the results do support past research suggesting that vitamin D plays some role in the disease, according to Nicholas LaRocca, vice president of health care delivery and policy research for the National Multiple Sclerosis Society, in New York City.
Sunlight triggers the body's synthesis of vitamin D, and some studies have linked both sun exposure and higher levels of vitamin D in the blood to a lower risk of multiple sclerosis.
No one knows if that's a cause-effect relationship. But clinical trials are underway to see whether vitamin D supplements can help slow MS progression, said LaRocca, who was not involved in the current study.
Until those trial results are in, it's too soon to make any specific vitamin D recommendations, according to LaRocca.
But, he added, since adequate vitamin D is important for overall health, people with MS could talk to their doctors about taking a supplement.
"They may be advised to have their vitamin D level tested first," LaRocca said.
The new findings support the theory that "avoiding sunlight" could be one of the triggers for MS, said study lead researcher Dr. Julie Laursen, of the Danish Multiple Sclerosis Center, in Copenhagen, Denmark.
Since sun exposure is closely connected to people's vitamin D levels, it's possible that the vitamin explains the later MS onset, Laursen said. However, she stressed, the findings do not "directly" support that.
The researchers found no relationship between MS onset and patients' reported use of multivitamins or vitamin D as teenagers.
According to Laursen, it's possible that sunlight, like vitamin D, has its own beneficial effects on the immune system.
In the study, adults with multiple sclerosis were asked about their "summer sun" habits and supplement use during their teens. They were also asked to recall their weight at age 20.
It turned out that MS arose later -- at the average age of 33 -- among people who'd gotten some sun every day as teenagers. Among people who'd gotten less sun, MS developed at age 31, on average.
People's weight at age 20 also seemed to matter: Those who'd been overweight developed MS almost two years earlier, on average, than those who'd been at normal weight at 20.
Body fat, Laursen explained, also happens to be related to vitamin D: People who are overweight tend to have lower blood levels of the vitamin.
Again, though, it's not clear that vitamin D explains the connection between weight and multiple sclerosis, Laursen said.
The study does, however, support the theory that adolescence is a critical time in MS development, according to Laursen. She said more research is needed to see whether there are roles for sun exposure, body weight, vitamin D, or all three.
LaRocca agreed. "It's a complex picture," he said.
In the meantime, LaRocca said, people can talk to their doctors about whether a vitamin D supplement is a good idea. They can also get the vitamin through certain foods, he added -- including fatty fish, and cereals and dairy products fortified with vitamin D.
The study findings were published in the journal Neurology.
Source: HealthDay Copyright © 2015 HealthDay (08/10/15)
Race and vitamin D levels may play a crucial role in the risk of multiple sclerosis (MS), according to Annette M. Langer-Gould, MD, PhD, of Kaiser Permanente in Pasadena, California.
Previous research has linked lower vitamin D levels with an increased risk of MS – but only in Caucasians. Langer-Gould and her team set out to see if the same could be said about African Americans and Hispanics. They looked at patients with newly diagnosed MS or clinically isolated syndrome (CIS), the precursor, between 2011 and 2014.
The researchers gathered data from 929 individuals (457 with MS/CIS and 472 healthy controls) through interviews, blood tests, and complete electronic health records. Patients and controls were matched for age, sex, and race/ethnicity:
Caucasian: 203 patients, 205 controls
African American: 108 patients, 116 controls
Hispanic: 146 patients, 151 controls
Overall, Caucasians had the highest levels of 25-hydroxyvitamin D (average of 70nmol/L) followed by Hispanics (55nmol/L) and African Americans (47nmol/L). Higher vitamin D levels were associated with lower risk of MS/CIS in Caucasians, especially those with levels over 75nmol/L. However, the findings did not show a correlation between vitamin D levels and MS/CIS risk in African Americans or Hispanics.
“A non-causal association cannot be excluded as vitamin D is a better surrogate measure of sunlight exposure in light than dark-skinned individuals,” the authors explained. “Another possible explanation is complex interactions between vitamin D and genotype as several genes that increase vitamin D bioavailability are more common in blacks.”
Prescribing vitamin D to prevent MS is premature, the team advises. The research reaffirms the importance of considering race in vitamin D studies.
Source: Specialty Pharmacy Times Copyright Specialty Pharmacy Times 2006-2015 Intellisphere, LLC (08/10/15)
Genzyme, has announced new five-year investigational data from the extension study of Lemtrada for patients with relapsing remitting multiple sclerosis (RRMS).
In RRMS patients treated with Lemtrada in the Phase III studies, the effects observed in the two-year trials were maintained through three additional years in the extension study.
The low annualized relapse rates observed in patients who received Lemtrada in CARE-MS I and CARE-MS II were maintained from year three to year five.
Through year five, 80 per cent and 76 per cent of patients who received Lemtrada in CARE-MS I and CARE-MS II, respectively, did not experience worsening of disability progression confirmed over six months as measured by the Expanded Disability Status Scale (EDSS).
Through year five, 33 per cent and 43 per cent of patients who had some disability before receiving Lemtrada in CARE-MS I and CARE-MS II, respectively, had improvement in EDSS score confirmed over at least six months as compared with pre-treatment baseline.
Through year five, patients who received Lemtrada in CARE-MS I and II experienced a slowing of brain atrophy as measured by brain parenchymal fraction on magnetic resonance imaging (MRI). In years three, four and five, the median yearly brain volume loss was -0.20 percent or less, which was lower than what was observed during the two-year pivotal studies.
In each of years three, four and five, most patients had no evidence of MRI disease activity (70 – 72 per cent, CARE-MS I; 68 – 70 per cent, CARE-MS II.)
Through year five, the incidence of most adverse events during the extension study was comparable or reduced compared with the pivotal studies. The frequency of thyroid adverse events was highest in year three and declined thereafter.
More than 90 percent of the patients who were treated with Lemtrada in the CARE-MS Phase III trials enrolled in the extension study. These patients were eligible to receive additional treatment with Lemtrada in the extension study if they experienced at least one relapse or at least two new or enlarging brain or spinal cord lesions.
“This data illustrates that most Lemtrada patients experienced sustained effects of treatment, despite the absence of additional treatment courses,” said Professor Eva Havrdová, MD, PhD, MS Center, Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic.
"It is encouraging to see consistent effects maintained across multiple meaningful outcomes through five years.”
Source: Business Wire ©2015 Business Wire (08/10/15)
Researchers say they have found a strong relationship between spinal cord grey matter atrophy with disability and multiple sclerosis, which they said was much stronger than the relationship for any known cortical grey or white matter metric.
The results were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Barcelona.
“This study was driven by the clinical observation that MS progression manifests as a progressive myelopathy in the majority of patients,” Regina Schlaeger, MD, study investigator from the department of neurology at the University of California, San Francisco, told Neurology Advisor.
“Our finding that the spinal cord grey matter was, among other conventional MRI metrics, most relevant in explaining disability was rather unexpected.”
For the study, Dr. Schlaeger and colleagues enrolled 142 patients with MS and 20 controls and scanned them with 3T MRI. The researchers acquired axial 2D phase sensitive inversion recovery (PSIR) images at disc levels C2/3, C3/4, T8/9 and T9/10. They segmented total cord areas (TCA) semi-automatically and spinal cord grey matter manually, and determined between group differences in areas with age and sex as covariates.
Compared with controls, cervical and thoracic spinal cord relapsing MS patients had smaller grey matter areas, although there were no significant differences in either spinal cord white matter area or TCA. Smaller grey matter areas were reported in progressive MS patients vs. relapsing MS patients, as were smaller TCAs.
Multivariable model results demonstrated the strongest correlation between cervical spinal cord grey matter area and Expanded Disability Status Scale (EDSS), followed by thoracic spinal cord grey matter area and brain grey matter volume.
In addition, researchers reported the following areas under the ROC curve for the prediction of a progressive course based on logistic models:
“Traditionally, spinal cord atrophy is thought to be mostly driven by axonal (white matter) loss. We found a preferential reduction in spinal cord grey matter in progressive patients and, moreover, a subtle but selective grey matter atrophy in relapsing patients,” Dr. Schlaeger said. “The cervical spinal cord grey matter area was strongly associated with disability (EDSS) and progressive phenotype, indicating that spinal cord grey matter atrophy is indeed clinically relevant. However, the validity of spinal cord grey matter assessments as a biomarker of progression needs to be further determined in longitudinal studies.”
Reference: Schlaeger R et al. Abstract 208. Presented at: The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress; Oct. 7-10, 2015; Barcelona.
Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (08/10/15)
In patients with primary progressive multiple sclerosis (PPMS), Gilenya resulted in similar mean percent brain volume change (PBVC) and per cent change in spinal cord area (PCSCA) vs. placebo, according to data from the INFORMS study.
“Anti-inflammatory strategies currently successfully applied in RRMS cannot be automatically translated into the PPMS population,” Özgür Yaldizli, MD, study investigator and neurologist from the UCL Institute of Neurology, Queen Square Multiple Sclerosis Centre, London, told Neurology Advisor.
“We need novel approaches to treat people with PPMS.”
Yaldizli presented the results at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Barcelona.
The catalyst for the analysis, Dr. Yaldizli said, was that in the past decade, studies have consistently shown that brain and spinal cord atrophy are more closely related to clinical disease progression in MS than magnetic resonance imaging (MRI) markers of inflammation. This led Dr. Yaldizli and colleagues to enroll 823 patients and follow them for three years. Patients were included if they had a clinical diagnosis of PPMS; disease duration of two to 10 years; and objective evidence of disability progression in the previous two years.
“Although the PPMS patients included in the INFORMS trial had a relatively low level of MRI-detected inflammation, the effect of Gilenya on MRI-markers of inflammation was consistent with that observed in RRMS patients,” Dr. Yaldizli said. “However, disappointingly, in INFORMS, there was neither a significant treatment effect on disease progression nor on brain or cervical spinal cord atrophy.”
Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (08/10/15)
A number of studies have previously suggested a negative effect of high cholesterol levels on the development of brain lesions in patients with multiple sclerosis, however, little is known about the effect of HDL (high-density lipoprotein) cholesterol, or “good” cholesterol, on MS.
Now, a team of scientists from the University of Buffalo has found that good cholesterol has protective properties for the blood-brain barrier. The study, Protective Associations Of HDL With Blood Brain Barrier Injury In Multiple Sclerosis Patients, has been published in the Journal Of Lipid Research.
“This finding is especially important because we found this protective effect very early in the disease,” said the study’s lead author Murali Ramanathan, PhD, a professor of pharmaceutical sciences in the UB School of Pharmacy and Pharmaceutical Sciences, and professor of neurology in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo.
To better understand the impact of HDL on MS, the team followed a group of patients for four years following their first experience of an attack of MS symptoms. The results offer a number of implications, not only in treatment discovery and development, but also in the drafting of future guidelines for MS prevention and management.
“This is the first time HDL cholesterol has been found to have such a clear benefit against the breakdown of the blood-brain barrier in MS patients,” said Dr Ramanathan.
“The breakdown of the BBB [blood-brain barrier] is the first step in the formation of brain lesions because it allows immune cells to enter the brain, form long-lasting lesions and mediate tissue injury.
“Cholesterol profiles can be affected by several factors including genetics, diet, smoking and physical activity. A better understanding of this key class of modifiable factors could be leveraged both as clinical advice to MS patients seeking to reduce the risk of progression and as the basis of guidance to healthy individuals with genetic and other known risk factors for MS.”
Source: Multiple Sclerosis News Today © 2015 BioNews Services, LLC (08/10/15)
A study has concluded that high-intensity exercise can improve muscles and stamina in people living with multiple sclerosis.
The study, High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile Characteristics and Exercise Capacity, a Randomised Controlled Trial by Inez Wens, Ulrik Dalgas, Frank Vandenabeele, Lotte Grevendonk, Kenneth Verboven, Dominique Hansen, Bert O. Eijnde, looked at three groups of MS patients.
One group were the sedentary control, while the other two groups performed high-intensity exercise – either continuously or at intervals – over a 12 week period.
The study concluded that 12 weeks of high intensity cardiovascular exercise in combination with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity, with interval training seemingly superior to continuous training.
Source:: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133697 (29/09/15)
Ireland’s Health Service Executive has agreed to fund ‘on a limited basis’ the cost of a drug that helps people with multiple sclerosis to walk.
The announcement that Fampyra is to be reimbursed under the State-funded drugs schemes follows a lengthy campaign by patients who say the drug has greatly aided their mobility.
The HSE says it is in the final stages of putting in place the arrangement around a “responder-based” reimbursement programme for Fampyra.
The cost of the drug will be covered where a demonstration of clinical response, based on objective criteria agreed with clinical experts, is recorded, it says. This clinical response must be shown to persist based on objective measurement at six-monthly intervals.
In 2013, the National Centre for Pharmacoeconomics, which rules on the cost-effectiveness of new drugs, found Fampyra would cost nearly €7,000 per patient each year. It said the €20 million annual cost to the State over five years would take money from other areas.
The HSE then decided that it could not approve the reimbursement of Fampyra and claimed the manufacturer, Biogen Idec, had failed to demonstrate or provide any formal justification for the prices proposed. Biogen maintained it had offered significant price reductions in the talks.
Agreement has now been reached on a reimbursement arrangement.
Patients have been paying up to €500 a month for Fampyra from their own resources after Biogen started charging for the drug last year following a free trial period.
Multiple Sclerosis Ireland expressed delight with the progress on reimbursing Fampyra, which it said had a significant impact on patients’ ability to remain independent.
Researchers from Queen Mary University of London (QMUL) are calling on the medical community to reconsider developing a known drug to treat people with relapsing-remitting MS after new evidence shows it does not increase the risk of cancer as previously thought.
The drug called Cladribine is already licensed and in use for people with leukemia. Previous studies, ran with patients at Barts Health NHS Trust in London, showed Cladribine to be highly effective in treating relapsing MS. One trial showed the drug reduced relapses by over 50 per cent, and nearly 50 per cent of people showed no signs of disease activity at all over two years. However, Cladribine was refused market authorisation on the suspicion it may cause cancer based on the interpretation of previous data.
A new study published in the journal Neurology: Neuroimmunology & Neuroinflammation compared the incidence of cancer where patients had been treated with Cladribine to other studies where they had been treated with other similar drugs that are currently licensed for MS.
The team from the Blizard Institute at QMUL compared data from the 11 pivotal trials that were used to support the licensing of seven different drugs to examine the cancer risk. They found there was no evidence for an increased risk of cancer in people with MS taking Cladribine.
Cladribine appears to be more effective, safer, easier to use and could potentially be cheaper than other current drugs used to treat MS.
“Our research shows that clinical academics and drug makers should continue to develop Cladribine for people with relapsing MS as the risk of developing cancer is no greater than for other types of current medication,” saidDr Klaus Schmierer, lead author and Reader in Clinical Neurology at QMUL and Consultant Neurologist at Barts Health NHS Trust.
He added: “As well as being easier and cheaper to administer, Cladribine benefits female patients who want to get pregnant. Other drugs used to treat relapsing MS need to be stopped during pregnancy and that can expose women to increased risk of MS disease activity. That’s not the case with Cladribine, which has a long lasting effect.”
It is estimated that over 120,000 people with MS live in the UK and it affects over two million patients globally. MS, which is a chronic, inflammatory condition of the central nervous system affects young adults and has a substantial impact on quality of their life, employment, and relationships.
Source: Queen Mary University of London, http://www.qmul.ac.uk/media/news/items/smd/164455.html 01/10/15
Two research teams say they may have found an unexpected way to prevent or treat the common virus found in many healthy people which can cause a rare but potentially lethal brain disease, progressive multifocal leukoencephalopathy (PML), in those with altered or weakened immune systems.
There have also been reported cases of PML in people taking the MS therapy Gilenya.
One team came up with a vaccine that can boost overall immune response against the virus, a prophylactic tactic to prevent the raging brain infection (Ray et al., 2015). Another group reports that an antibody mix engineered from PML survivors may be a promising treatment for those who develop PML (Jelcic et al., 2015). The two papers were published together online in the journal Science Translational Medicine.
The new studies use too few patient samples and test cases to be definitive, but the results position both strategies for the next step of clinical testing, say the authors and others interviewed by MSDF. Independent of the potential therapeutic application, the findings also add fuel to a debate about the underlying mechanism of PML.
Concern about PML discourages people from choosing a highly effective treatment for RRMS and limits the time they can take it, said David Clifford, MD, a clinical neurologist at Washington University in St. Louis, Missouri, U.S., who was not involved in the new studies.
A 2005 report linked PML with monoclonal antibody therapy, specifically Tysabri, in two people with MS and one with Crohn’s disease. Tysabri blocks a receptor on T cells and prevents them from crossing from the blood into the brain. The drug was withdrawn from the market for one year.
PML prevention now relies mainly on prescreening high-risk patients and prescribing Tysabri for only a limited time, as well as close monitoring of people on any drug associated with PML.
Research in the small PML field has focused on the clear central role of T cells and the way the virus enters brain cells and replicates. Evidence from people with MS seemed to confirm that antibody-based immunity is nearly worthless in PML.
“You have to look at the right kind of antibodies,” said Diana Pastrana, PhD, a senior staff scientist in Buck’s lab and co-author of the paper, referring to specific neutralizing antibodies of JCV variants. They hypothesised that PML may arise from JCV mutants that evade the immune system.
To investigate that possibility, they started with cell assays. Serum from PML patients neutralised the wild-type JCV but not the JCV mutants commonly found in the brains of people with PML. In contrast, most of the serum from healthy people effectively neutralized all JCV types.
In mice, the researchers were able to close these antibody “blind spots” to the JCV mutants with a general vaccine made of virus like particles (VLP). The same VLP technology is used in the HPV vaccine and others on the market now.
The premise of the two papers rests on the assumption that the virus replicates and mutates, leading to PML. In the brains of people who have died from PML, scientists have found mutations in the JCV protein shell. Scientists still don’t know whether the surface mutations help JCV enter the brain and cause PML or whether the protein shell evolves when virus already in the brain goes wild in the absence of T cells.
The active and passive vaccination discoveries are protected by patents
Despite the interest of drug companies in preventing PML, the disease is so rare that they may hesitate to launch an expensive clinical trial, several experts told MSDF.
Source: Multiple Sclerosis Discovery Forum, http://www.msdiscovery.org/news/new_findings/22160-studies-propose-vaccination-troublemaking-virus, by Carol Cruzan Morton 02/10/15
Transcranial direct current stimulation (tDCS) may help improve cognition and reduce mental fatigue in patients with multiple sclerosis (MS), results from a pilot study indicate. The findings were presented at theAmerican Neurological Association 2015 Annual Meeting in Chicago. Tracy D. Vannorsdall, PhD, of Johns Hopkins University School of Medicine, and colleagues conducted the small study in five patients with secondary progressive MS. The findings, while preliminary, show promise for tDCS as a future therapy for MS.
In a sham-controlled, single-blind crossover experiment, participants completed cognitive assessments (MAC-FIMS cognitive battery, Beck Depression Inventory II, and Fatigue Severity Scale) both before and after receiving 2 MA of anodal and sham tDCS to the left dorsolateral prefrontal cortex for 30 minutes, once a day for five consecutive days, while also performing cognitive rehabilitative tasks. There was a four-week washout period between therapies.
Those who received active stimulation showed a reduction in fatigue while an increase in fatigue was observed during sham stimulation. Results also showed a statistically significant improvement in verbal short-term memory, learning, and memory, and positive trends were also seen in working memory and other cognitive skills during active stimulation compared to sham stimulation. No change in depression scale ratings was observed for either therapy.
Overall, tDCS was found to be safe and well-tolerated, with results suggesting that it may ameliorate fatigue and cognitive dysfunction in MS.
Source: Neurology Advisor, http://www.neurologyadvisor.com/ana-2015-coverage/transcranial-direct-current-stimulation-multiple-sclerosis-treatment/article/442238/, by Alicia Ciccone, 01/10/15
Smoking is a risk factor for developing MS among first-degree relatives of confirmed MS patients, according to an ongoing study of more than 2,600 individuals.
The study, based on a model combining genetic and environmental risk factors to identify likelihood of developing MS, found in 1,696 first-degree relatives of MS patients that smoking is associated with MS susceptibility, said lead study author Zongqi Xia, MD, PhD, of Brigham and Women's Hospital in Boston.
The work, presented at the American Neurological Association's annual meeting, did not find an association between infectious mononucleosis and risk of MS, which was of interest because past studies have linked MS to exposure to Epstein-Barr virus which causes infectious mononucleosis.
The investigators found the incidence of MS in this population to be 123 per 100,000 -- a rate that is 20 to 30 times higher than that of the general population, Xia said. Consequently, the model holds promise for identifying individuals at the highest risk of developing MS who could be good candidates for prevention efforts.
"There is a great unmet medical need, which is there is currently no primary prevention strategy for multiple sclerosis," Xia said. This is due to several factors, he said, including that the risk factors and incidence of MS in a high-risk population are not well characterized. In addition, he said, "We do not have a good, reliable set of tools to identify those high-risk individuals, particularly at an early stage of the disease."
Through the Genes and Environment in Multiple Sclerosis (GEMS) project, Xia said he and his colleagues hope to establish a platform to map a sequence of events that lead to the onset of disease, capturing the transition from good health to disease state. Their ultimate goal, he said, is to test primary prevention strategies in this population.
Xia and colleagues created a formula to assess each study participant's Genetic and Environmental Risk Score (GERS), which incorporates presence of 64 genetic variants reported to have an association with MS, as well as three environmental factors reportedly associated with MS: female gender, smoking status, and history of infectious mononucleosis.
Source: MEDPAGE TODAY, http://www.medpagetoday.com/MeetingCoverage/ANA/53892, by Karen Blum, 04/10/15
The first electronic automatic injector to deliver a drug for the most common form of multiple sclerosis has received approval from the America’s Food and Drug Administration.
The injection delivers Betaseron, a disease-modifying drug approved 22 years ago by the FDA for relapsing forms of the incurable, often disabling disease of the central nervous system.
The new device, called Betaconnect, will be available in early 2016, said Bayer AG, which developed the injector and sells the drug.
The original device, through which Betaseron is delivered, was mechanically activated and makes a discernible sound during administration, which tends to disconcert patients, according to Amy Ross, former president of the International Organization of MS Nurses in America.
This new autoinjector, already available in Europe, reminds patients to take their medicine every other day, and is silent when used. It is customizable, allowing for adjustments in speed and depth of the injection, and has automatic needle retraction.
Although a sizable share of the MS market in the United States has been captured by oral drugs, including Biogen Tecfidera, reports linking some treatments to serious brain infections have tempered enthusiasm.
Doctors are now starting patients on injectable therapies - with an eye on long-term safety and efficacy - because many of these patients are quite young, said Ross, estimating about 50 per cent to 60 per cent of patients today are diagnosed in their 20s and 30s.
Source: Medical Daily © 2015 Medical Daily (28/09/15)
Genentech, a member of the Roche Group, has announced positive results from a pivotal Phase III study that evaluated ocrelizumab in people with primary progressive multiple sclerosis (PPMS). The study (ORATORIO) met its primary endpoint, showing treatment with ocrelizumab significantly reduced the progression of clinical disability sustained for at least 12 weeks compared with placebo, as measured by the Expanded Disability Status Scale (EDSS).
Overall, the incidence of adverse events associated with ocrelizumab was similar to placebo; the most common adverse events were mild-to-moderate infusion-related reactions. The incidence of serious adverse events associated with ocrelizumab, including serious infections, was also similar to placebo.
“People with the primary progressive form of MS typically experience symptoms that continuously worsen after the onset of their disease, and there are no approved treatments for this condition," said Sandra Horning, M.D., chief medical officer and head of Global Product Development.
“Ocrelizumab is the first investigational medicine to show a clinically meaningful and statistically significant effect on the progression of disease in primary progressive MS.”
The positive study results observed with ocrelizumab in both people with PPMS (ORATORIO) as well as those with relapsing forms of MS (in the studies OPERA I and OPERA II) validate the hypothesis that B cells are central to the underlying biology of the condition.
Genentech plans to pursue marketing authorization for ocrelizumab in relapsing MS and in PPMS. Data from the OPERA I and II studies and from the ORATORIO study will be submitted to the U.S. Food and Drug Administration in early 2016.
Source: Business Wire © 2015 Business Wire (28/09/15)
The discovery that specific antibodies play a key role in combating the viral infection progressive multifocal leukoencephalopathy (PML), a vaccine against the disease could now be developed, say researchers.
Humans carry a multitude of viruses and bacteria in their gut, on their skin and in other organs. Often, these are involved in important bodily functions. Under certain conditions, however, some can also cause diseases. The JC virus, a member of the polyoma tumor virus family, is a prime example. This pathogen was first isolated from the brain of a patient who was suffering from PML. The virus, which more than 60 percent of the global population are infected with, normally resides in the kidneys and certain other organs. JC virus can trigger the PML infection in the brain, which, in most cases, is fatal.
Two studies conducted by an international team of researchers from the University of Zurich, the University Hospital Zurich, the National Institutes of Health in the USA, San Raffaele Hospital in Milan, the University of Tübingen, and the UZH spin-off Neurimmune now reveal that the antibodies in PML patients often fail to recognize the JC virus they are infected with.
"In healthy people, the disease never breaks out as the immune system keeps it well under control. Once the immune system is compromised, however, such as in patients with tumors, leukemia, AIDS, autoimmune diseases and certain immunosuppressive treatments, the JC virus is able to alter its genetic information and infect the brain," explains Roland Martin, professor of neurology at the University of Zurich.
In MS patients, the treatment with a particular antibody, Tysabri, prevents immune cells from reaching the brain - but at the same time, also inhibits the brain's immunosurveillance. If JC viruses enter the brain during the treatment, they go undetected, which can cause PML. Over 560 MS patients worldwide have already developed the PML brain infection.
By vaccinating mice and a PML patient with the virus' coating protein, the international groups were able to demonstrate that the antibody response was so strong that the patient was soon able to eliminate the JC virus. The so-called active vaccination method was developed at the University of Zurich and the University Hospital Zurich, and has already been used successfully on two more patients. The JC-virus-specific antibodies that are of interest for the treatment of the existing brain infection were developed by the group at the University of Zurich and the University Hospital Zurich together with colleagues from the University of Tübingen and the biotechnology company Neurimmune in Schlieren.
"We made a major breakthrough," says Martin. "We managed to isolate antibody-producing cells from a patient who survived PML and use them to produce neutralizing antibodies against the JC virus. These human antibodies have a major advantage: they recognize the most important mutants of the JC virus that can cause PML. They now make promising candidates for the development of a treatment for PML."
Source: Advantage Business Media © Copyright 2015 Advantage Business Media (25/09/15)
Researchers recommend extending the minimum timeframe for confirming disability progression in multiple sclerosis (MS) from three–six months to 12 or 24 months to better distinguish true irreversible disability from relapse-associated transient disability.
The recommendation is based on their finding that a three-six month confirmation period overestimated the accumulation of permanent disability by up to 30 per cent, compared with up to 20 per cent and 11 per cent if a 12-or 24-month period is used, respectively.
“This could lead to spurious results in short-term clinical trials, and the issue may be magnified further in cohorts consisting predominantly of younger patients and patients with relapse-remitting disease,” says the team.
Led by Tomas Kalincik (Royal Melbourne Hospital, Australia), the researchers used the global MSBase registry to evaluate 48 criteria for disability progression in 16,636 patients with MS who had a minimum of three Expanded Disability Status Scale (EDSS) scores recorded.
The median time between EDSS visits was 6.6 months and the cumulative captured follow-up was 112,584 patient–years, with a median follow-up per patient of 5.7 years.
Progression rates varied between 0.41 and 1.14 events per patient-decade with only 17.3 per cent of progression events identified by all 48 criteria simultaneously.
Over the subsequent 5 years, disability regressed in 11 per cent to 34 per cent of the progression events. The length of the disability confirmation period was the most important determinant, with the proportion of events regressing within five years decreasing with longer confirmation time, from 30 per cent at three months to 26 per cent at six months, 20 per cent at 12 months and 11 per cent at 24 months.
Indeed, a 12- or 24-month confirmed progression of disability combined with a baseline EDSS recorded at a single timepoint provided the most stable criteria for detecting disability progression and persistence at five years, correctly identifying 80–81% and 88–89% of persistent progression events, respectively. The two-strata and three-strata EDSS criteria for determining the magnitude of progression were comparable for identifying persistent progression events.
The researchers note in Brain that progression events confirmed for 3 months were the least persistent, with 22–26 per cent of such events regressing over the initial 10 years after progression, compared with just eight-nine per cent of those confirmed over a 24-month period.
Other factors increasing the likelihood of a progressive disability event were male gender, older age, progressive MS and a lower EDSS score, while regression of disability was more likely to occur among women, younger individuals and those with a relapse–remitting disease course.
Given their findings, Kalincik and colleagues recommend “implementation of longer disability confirmation period in the design of observational studies but also of prospective clinical trials.”
They add: “This is not impractical as most modern trials include open-label extension studies, and these observations can be used to define 12- and 24-month confirmations of disability progression events which occurred during the randomised stages of these trials.”
Source: News-Medical.Net Copyright 2000-2015 AZoM.com Limited (24/09/15)
In a new study entitled “LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice”, scientists report that the loss of myelin in MS patients’ brains contributes to their cognitive impairment. They showed that inhibiting protein LINGO-1 can improve these cognitive deficits by promoting myelin growth, thereby establishing impairment of LINGO-1 as a potential new therapeutic avenue for cognitive deficits in MS patients.
The study was published in the journal Science Reports.
The researchers used mouse models for human MS, specifically the experimental autoimmune encephalomyelitis (EAE) mouse model, to investigate the link between myelin impairment and cognitive decline. Moreover, despite the high incidence of cognitive impairment in MS patients, the treatments available have no benefits in improving patients’ cognitive features. Hence, there is an unmet need for an effective treatment.
In the study, researchers observed that the deficits in both memory and learning skills occur at later stages of the disease. They followed previous studies suggesting that a protein called LINGO-1 (short for LRR and Ig domain containing NOGO receptor interacting protein 1) inhibits myelin production. Accordingly, the team used an antibody against LINGO-1 and discovered it significantly improved learning and memory in the EAE mouse model, while it activated the AKT/mTOR signaling pathway, a crucial regulator of myelin growth. This phenotype was accompanied by an increase and restoration of myelin basic protein (MBP) expression in the brain of these mice, a key protein in the myelination process of nerves.
These findings therefore suggest that demyelination may contribute to the learning and memory deficits of MS patients, and establish the potential action of LINGO-1 antibody as a strategy to promote myelin growth. Hence, inhibiting LINGO-1 protein is a potential future treatment for cognitive impairment in MS patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (24/09/15)
In a review published in the European Journal of Neurology, A. P. Lysandropoulos from the University of Brussels and E. Havrdova, from the University of Prague described some ‘hidden’ issues that influence the quality of life (QoL) in patients with MS.
In the review, researchers discussed the limitations concerning the measurement of QoL and provide early evidence for the benefits of specific psychological support on patients’ QoL.
QoL in patients with MS is influenced by factors beyond pathophysiology and disease progression, and is frequently at odds with objective measures of condition. MS patients may be well treated and free of symptoms but still have poor QoL due to patient-centred factors such as depression, inability to work and relationship issues.
In the review, “Hidden factors influencing quality of life in patients with multiple sclerosis”, the researchers firstly mentioned that amongst the first critical parameters influencing QoL in MS patients is the MS ‘label’. The mere thought of MS can strike fear in people even in the absence of any knowledge about the disease. At the time of an MS diagnosis, many patients immediately visualise themselves in a wheelchair, and this pessimistic perception of the condition determines the way in which a patient analyses his or her symptoms by amplifying them.
Cognitive impairment is another factor that is increasingly being recognised as part of life with MS, existing alongside physical symptoms and limitations. Since patients become less effective professionally and socially, impaired cognition can lead to a vicious cycle of frustration with negative impact on QoL. Cognitive issues can develop early in the course of MS, particularly with respect to processing speed and handling of complex information.
Sexual dysfunction is also frequent in MS patients, and it is reported to occur in up to three-quarters of women and up to 90% of men. Sexual dysfunction has been shown to have a greater detrimental effect on mental health aspects of health-related QoL in MS patients than the severity of physical disability.
Regarding MS as a family problem, a diagnosis of MS is traumatic not only for the patient but also for the patient’s family. Most MS patients are diagnosed at a relatively young age and it is only natural for parents to be concerned about their child. Life plans such as work, relationships and family planning may be adversely affected by MS, and feelings of anger, denial and fear are not limited to the patient but are also experienced by the family.
A real limitation regarding the measurement of QoL in MS patients is the lack of validated instruments. Traditional approaches used to measure QoL in MS tend to lack sensitivity to change, and the current repertoire of tools does not allow for easy assessment of all aspects of the disease, including the many hidden issues that influence QoL.
Physical and cognitive difficulties have a negative psychological impact on MS patients and, in turn, on their QoL. Psychological interventions for MS are necessary to address all the factors that influence QoL in patients. The beneficial effects of psychological support in MS patients may go beyond improved patient-centered outcomes and impact directly on disease activity.
The authors believe that, as with other chronic diseases, it can be argued that QoL is a more relevant outcome in MS patients than traditional measurements such as disability or neurological impairment. However, much work needs to be done before QoL assumes its rightful position as the primary outcome measure in clinical trials and clinical practice. According to the authors, elements that influence QoL in MS patients need to be better defined and there is a need to be clarified which of the many QoL instruments should be used and for what purposes. Moreover, the authors mentioned that more evidence is required of the benefits of psychological support strategies on both disease progression and QoL in MS patients.
The authors concluded that future studies are expected to better define the most suitable means of assessing patient-centered outcomes in MS, and identify the most appropriate management strategies for individual patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (22/09/15)
An encouraging new analysis reveals Gilenya is an effective MS therapy for a treatment period of up to three years. The results were presented at the Annual Meeting of the Consortium of MS Centres in America.
Gilenya, produced by Novartis, is an immunomodulatory drug able to reduce the rate of relapse in relapsing-remitting MS (RRMS) patients.
In the study, the team analysed data from three previously published phase 3 clinical trials (FREEDOMS, FREEDOMS II and TRANSFORMS) that assessed the use of Gilenya in RRMS patients compared to beta interferon or a placebo. The team found Gilenya 0.5 mg offered consistent clinical benefits to RRMS patients in comparison to placebo or beta interferon, irrespective of when the patient had the first symptom of the condition or the number of years of previous treatment.
The team reported that overall, Gilenya was able to significantly reduce the annualised relapse rate in patients with zero, less than three, and more than three years of therapy in comparison to placebo and beta interferon.
“We weren’t able to find any larger subgroup of patients who didn’t respond well,” said Dr. Daniel Ontaneda, assistant professor of medicine and neurology at the Cleveland Clinic, who presented the data.
“One might have had an intuition that patients over age 40, say, weren’t going to respond. But the clinical take-away is that the medication works equally well for almost everyone.”
The efficacy of Gilenya represents good news for the MS population, however, neurologists still have the difficult task of determining which of the currently available MS medications should be prescribed to a particular patient.
“We now have 12 available medications for MS,” noted Dr. Ontaneda. “For clinicians, the decision on which medication to prescribe is becoming ever more complex. We need to figure out if there are advantages for one type of patient versus another. Trying to identify responders and non-responders is something we need to continue to pursue.”
According to Dr. Timothy L. Vollmer from the University of Colorado School of Medicine, who was not involved in the study, the findings go against the position taken by a report from the Agency for Health Care Research and Quality (AHRQ). “The AHRQ consensus document said there is no evidence of drug benefit beyond two years,” said Dr. Vollmer.
“This study will push back against some of those insurer groups and the AHRQ. It’s consistent with what we’ve all been saying, that we don’t see any loss of efficacy in patients kept on Gilenya for a long time.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (22/09/15)
People living with multiple sclerosis who are required to undergo assessments to claim disability benefits are having their health damaged as a result, reports The Guardian.
The MS Society found that nearly half (48 per cent) of people with the disease of the nervous system who had an assessment for Employment Support Allowance (ESA) felt the process caused their condition to deteriorate or relapse. Just over a third who had a face-to-face assessment for Personal Independence Payment (PIP) said the same.
The charity says the disability benefits system fails to take adequate account of the fluctuating and hidden symptoms of MS, or the extent of their impact. Chief executive Michelle Mitchell said: “Having MS is enough; it should not be made harder by a welfare system that doesn’t make sense for people living with the condition.
“Lack of understanding of the condition and the failure to use information from medical professionals is causing stress or contributing to relapses and deteriorating health. This is counterintuitive to a system designed to support people with disabilities.”
ESA, and its eligibility test, Work Capability Assessments, and PIP have been dogged by controversy. The fairness of the assessments have been called into question repeatedly and there have been severe delays in processing claims, leaving people stressed and penniless while they wait. As well as the detrimental impact on health recorded by the survey, a number of respondents said the changes to the benefits system had forced them to spend less, including on treatment.
Around one in ten said they had reduced outlay on attending hospital appointments and a similar proportion said they had cut down on medical treatment or prescriptions. About a third said they were spending less on food, 28 per cent on transport and 41 per cent on socialising with family and friends. Under the welfare reform and work bill, currently going through the committee stage in the House of Commons, people considered capable of work at some point in the future or of beginning to move into work immediately will see their ESA reduced.
Michelle said: “Living with a chronic, disabling, neurological condition such as MS is hard – it is also expensive. There are often substantial extra costs which add an average of £200 a week to the household bills. Steps must be taken to make sure the disability benefits system is working for those who rely on it or people with MS will continue to struggle.”
A spokesman for the Department of Work and Pensions said: “We understand that going through the assessment process can be difficult for people suffering from conditions such as MS and our staff work hard to make it as straightforward as possible.
“The purpose of an assessment is to identify the support that a claimant needs and they are carried out by registered and experienced health professionals. Our staff receive training and guidance for a range of medical conditions including fluctuating conditions such as MS.”
Between 2013 and 2014, MS-UK experienced a 23% increase in the amount of people who use the MS-UK Helpline, and benefits is one of the top three subjects people contact the Helpline about.
For support today, contact the MS-UK Helpline on freephone 0800 783 0518 or via our live webchat service http://www.ms-uk.org/livewebchat
Source: The Guardian © 2015 Guardian News and Media Limited (14/09/15)
German healthcare firm Merck has announced it is to submit its investigational treatment Cladribine Tablets for the treatment of relapsing MS for registration in Europe. The decision follows the company’s evaluation of new data and additional analyses of the compound’s benefit-risk profile.
Merck has submitted a letter of intent to the EMA to file a Marketing Authorization Application (MAA) for Cladribine Tablets, which initiates a process to address a number of pre-submission requirements.
“I applaud Merck for its decision to move forward with Cladribine Tablets as demonstrated in its Letter of Intent to the European Medicines Agency,” said Professor Giancarlo Comi, director of the Institute of Experimental Neurology (INSPE) and of the department of neurology at San Raffaele Hospital in Milan, Italy. “This decision is very positive for patients with multiple sclerosis because tailoring treatment to their individual needs is a key strategy for optimizing their care, and to achieve this we need to have access to more therapeutic options. While the options available to treating neurologists have grown over the years, Cladribine Tablets have the potential to offer a truly innovative addition to the armamentarium physicians have at their disposal to treat their patients."
“Time has brought additional data that allows a better characterisation of the benefit-risk profile of Cladribine, and this has driven our decision to move forward with the registration process,” said Belén Garijo, of the executive board of Merck and CEO Healthcare.
Merck wound down its clinical development program for Cladribine Tablets in 2011 after some regulatory authorities expressed concerns over the insufficient characterisation of the drug's benefit-risk profile. Nevertheless, several large clinical trials were allowed to complete and additional safety information was also collected in a long-term registry.
Source: Merck © Merck KGaA, Darmstadt, Germany (11/09/15)
In the first study of its kind, researchers at the Centre for BrainHealth at The University of Texas at Dallas and UT Southwestern Medical Centre found that individuals with multiple sclerosis (MS) have decreased connectivity between key regions of the brain, slowing their cognitive speed and leading to impairments in concentration, attention, memory and judgment.
The findings have been published in Neuropsychology.
“Our study is the first to really zero in on the physiology of cognitive speed, the central cognitive deficit in MS,” said Dr. Bart Rypma, Center for BrainHealth principal investigator, who also holds the Meadows Foundation Chair at UT Dallas.
“While white matter is essential to efficient network communication, white matter degradation is symptomatic of MS. This study really highlights how tightly coupled connectivity is to performance and illuminates the larger, emerging picture of white matter’s importance in human cognitive performance.”
In the study, MS patients, compared to non-MS individuals, showed weaker brain connections between the dorsolateral prefrontal cortex, which is responsible for executing goal-directed thought and action, and posterior brain regions, which carry out tasks related to cognitive speed, such as visual processing, motor execution and object recognition.
Researchers, collaborating with Dr. Elliot Frohman, director of the multiple sclerosis program and clinical center at UT Southwestern, recruited 29 participants with relapsing-remitting MS and 23 non-MS patients. Participants underwent functional magnetic resonance imaging (fMRI) while completing a test of cognitive processing speed.
Participants were given four seconds to view a nine-item key of number and symbol pairs and one number-symbol pair probe. Participants were asked to indicate whether the probe appeared in the key.
While accuracy was similar for both groups, response times for MS patients were much slower. Analysis of the fMRI data revealed that while completing this measure, MS patients showed weaker functional connections with the dorsolateral prefrontal cortex.
“These findings reveal a diffuse pattern of disconnectivity with executive areas of the brain,” said Nicholas Hubbard, the study’s lead author and a doctoral candidate at the Centre for BrainHealth working with Rypma.
“Importantly, these decreases in connectivity predicted MS-related cognitive slowing both in and out of the fMRI environment suggesting that these results were not specific to our task, but rather were able to generalize to other situations where cognitive speed is required.”
The research supports the need for therapies that target white matter structures and white matter proliferation. Rypma and Hubbard are further exploring the physiology of white matter to better understand cognitive speed reductions not only in MS patients, but also in healthy aging individuals.
Source: UT Dallas News Center © 2015 The University of Texas at Dallas (11/09/15)
Melatonin could help treat MS(11/09/15)
Insomniacs and world travelers alike use melatonin—a hormone that regulates the body’s internal clock—to help them fall asleep and get some extra shuteye. Now, a new study shows that the “sleep hormone” may also give relief to patients with multiple sclerosis.
A possible environmental factor in the cause of MS could be changes in the seasons, says Mauricio Farez, a neurologist at the Raúl Carrea Institute for Neurological Research in Buenos Aires, and after he and colleagues noticed fewer MS flare-ups took place in the fall and winter—the time of year that melatonin production is at its peak.
Melatonin levels depend on sunlight exposure, so seasonal changes cause the hormone to fluctuate; less sunlight in the fall and winter increases melatonin, whereas more sunlight during spring and summer decreases it.
To test the “seasonal” effect of melatonin on MS patients, the researchers monitored 139 MS patients for a year, tracking relapse rates and levels of a small molecule in melatonin called 6-SM. They saw that during fall and winter, patients’ relapse rates were 32 per cent lower than the rest of the year, when melatonin levels naturally dip.
Thinking the immune system likely played a key part, the scientists hypothesised that the increase in melatonin led to an increase in defensive bodies known as T regulatory cells, which work by secreting protective proteins that keep rogue immune cells in check. At the same time, melatonin activates a protein that blocks production of the harmful T cells. The researchers then confirmed their hypothesis in mice: When they dosed the animals with melatonin, the rodents ramped up their production of protective T cells and reduced their concentrations of harmful cells.
The team saw similar effects in in human cells in the lab, reports online today in Cell. “Our research explains something that wasn’t known before in terms of how multiple sclerosis is modulated by the environment,” says co-author Francisco Quintana, a neurologist at the Ann Romney Centre for Neurologic Diseases at Brigham and Women’s Hospital in Boston.
Although the findings are a step in the right direction, the link between melatonin and the immune system still lacks some important details. Researchers have yet to pinpoint, for example, how helper T cells protect the myelin sheath from misguided immune attacks. Farez says he and his colleagues plan to explore that process more in the future.
But other researchers caution against getting too absorbed in one single mechanism of an extremely complicated disease. “This group is enthusiastic about the role of [rogue cell] Th17, and so am I, but it’s only part of the story,” says Lawrence Steinman, a neurologist at Stanford University in Palo Alto, California, who specializes in MS.
Follow-up clinical research should target a larger, more inclusive population, experts say. The current study included only patients from Buenos Aires. Farez says a diverse geographic sample is important to ensure melatonin has the same effects on patients in places with different amounts of seasonal daylight.
But the team’s main concern doesn’t have to do with experimental setup. It has to do instead with the knock-on effects of publishing such research. Melatonin is widely available as an over-the-counter sleep aid, and they worry that some MS patients might use the hormone as a supplemental treatment. “We don’t want patients to see the study and misinterpret our results,” Farez says. “It’s a neat study and great data, but we still need to do a lot of work.”
Source: AAAS Science © 2015 American Association for the Advancement of Science (11/09/15)
In a new study entitled Neutrophil Trails Guide Influenza-Specific CD8+ T Cells In The Airways, researchers have uncovered a key mechanism mediated by neutrophils that guides immune system cells to the site of an injury or infection.
These findings are particularly relevant to the study of autoimmune diseases such as multiple sclerosis, since blocking immune cells from migrating and attacking healthy tissue may disrupt the progression of these conditions.
The study was published in the journal Science.
The influenza virus infects the layer of cells that line the respiratory tract. When infection occurs, cells of the immune system must be able to travel and reach the site of infection to eliminate the infected cells. Crucial players in the immune system for eliminating viruses are effector T cells. However, how these cells are guided and able to reach their final destination, either at the site of an injury or infection, is poorly understood.
In this new research, a team of scientists investigated how effector T cells are guided to the site of infection and discovered that this is achieved with the help of cells called neutrophils – a key player of the immune system and the first cells responding to infections. Neutrophils are the most abundant type of white blood cells of the immune system and are highly motile. The authors observed that neutrophils arrive rapidly (within one hour) to the site of infection and discovered that these migrating cells leave a long-lasting “trail” enriched in a chemokine, CXCL12. Chemokines are small protein molecules secreted by cells to “attract” other cells, in this case the effector T cells. When the team specifically removed the CXCL12 signalling, they discovered that T cells were unable to reach the site of infection so easily and that the ones who did were less efficient.
Minsoo Kim, Ph.D., study lead author and associate professor of Microbiology and Immunology at the School’s David H. Smith Centre for Vaccine Biology and Immunology noted in a news release: “Immune cells team up and share information to get their job done, much like many types of animals take part in collective behaviours to benefit the group as a whole.”
David J. Topham, Ph.D., co-author and the Marie Curran Wilson and Joseph Chamberlain Wilson Professor of Microbiology and Immunology added, “Understanding how immune cells collaborate to arrive at the site of an infection will lead to new ways to control and improve the body’s response to all types of illnesses.”
In multiple sclerosis and lupus, two autoimmune diseases, immune cells migrate and attack healthy tissue. These new findings may also underlie autoimmune disease pathogenesis, and so blocking neutrophil-mediated CXCL12 release may benefit multiple sclerosis and lupus patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (10/09/15)
‘Smoking impacts on multiple sclerosis’(10/09/15)
Patients with multiple sclerosis are at raised risk of their disease progressing if they continue to smoke, new research suggests.
Cigarette smoking is a known risk factor for multiple sclerosis, according to Dr Jan Hillert of the Karolinska Institutet in Stockholm, Sweden, and colleagues writing in JAMA Neurology. Disease development is 20 per cent to 50 per cent more likely in smokers than non-smokers, "making it a strong avenue for influencing patient outcomes".
Previous studies "have not specifically assessed the period after diagnosis or whether continued smoking affects the disease course", claim the team, so they investigated further. They carried out a study of 728 multiple sclerosis patients who smoked at diagnosis.
Analysis showed that "each additional year of smoking after diagnosis accelerated the time to secondary progressive disease by 4.7 per cent". They add: "Those who continued to smoke continuously each year after diagnosis converted to secondary progressive disease faster than those who quit smoking, reaching secondary progressive disease at 48 and 56 years of age, respectively."
They wrote: "We propose that patients with multiple sclerosis should be advised to stop smoking once a diagnosis has been made, not only to lessen risks for comorbidities, but also to avoid aggravating multiple sclerosis-related disability. Health care services for patients with multiple sclerosis should be organised to support such a lifestyle change."
In an editorial, Dr Myla Goldman of the University of Virginia, USA, added: "Even after multiple sclerosis diagnosis, smoking is a risk factor worth modifying."
Ramanujam, R. et al. Effect of Smoking Cessation on Multiple Sclerosis Prognosis. JAMA Neurology 9 September 2015 doi:10.1001/jamaneurol.2015.1788.
Source: Englemed Health News copyright Englemed Ltd 2015 (10/09/15)
New genetic risk factors identified(10/09/15)
Two new risk factors for multiple sclerosis have been identified by a research group at the Wellcome Trust Centre for Human Genetics at the University of Oxford in the United Kingdom.
Led by Dr. Loukas Moutsianas, the team discovered that having key gene allele interactions (each of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome - specifically HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02 in this case )put an individual at risk for developing multiple sclerosis. The findings were outlined in a study published in the prestigious journal Nature Genetics, entitled “Class II HLA Interactions Modulate Genetic Risk for Multiple Sclerosis.”
The research team was working off of previous knowledge that human leukocyte antigen (HLA) alleles — specifically, the HLA-DRB1*15:01 allele — dominate a patient’s risk factor for developing multiple sclerosis. There is some evidence that HLA alleles interact with each other in other neurological disorders, but such a phenomenon had not been reported for multiple sclerosis.
After constructing a model of HLA risk for multiple sclerosis, the researchers were able to create a high-resolution map of HLA risk for the condition. Agreeing with previous literature, the team found that HLA-DRB1*15:01 increased the risk for multiple sclerosis nearly four-fold. There was an additive risk for certain alleles, while other alleles seemed to be protective.
Studies such as this one define additional risk factors for multiple sclerosis that may help identify patients with the disease more accurately than other risk factors. If an individual suspected to have multiple sclerosis had their genes sequenced, they could know if they were indeed at a higher risk for multiple sclerosis and continue with additional diagnostic tests.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (10/09/15)
Japanese scientists have discovered new information about how the myelin sheath is repaired following damage.
The study, titled “Inactivation of Protein Tyrosine Phosphatase Receptor Type Z by Pleiotrophin Promotes Remyelination through Activation of Differentiation of Oligodendrocyte Precursor Cells,” appeared in the Journal of Neuroscience on September 2, 2015.
The symptoms of multiple sclerosis are due to an immune attack on the body’s own myelin. When myelin is lost around nerve cells, this can cause unpredictable loss of movement, sensation, vision problems and feelings of pain. Myelin is made by special nervous system cells called oligodendrocytes. Although it is well-known that myelin can be repaired by oligodendrocytes if it is damaged scientists do not understand the exact repair mechanisms used by these cells. In MS, myelin unfortunately does not appear to be easily repaired, also for unknown reasons.
The researchers, led by Professor Masaharu Noda and colleagues of the National Institute for Basic Biology, wanted to study how myelin is repaired in mice with an experimental form of MS, induced by the myelin-damaging drug cuprizone. They studied both normal mice and genetically-altered mice that lacked protein tyrosine phosphatase receptor type Z (PTPRZ), which is a protein that may cause oligodendrocytes to turn into mature cells, rather than stay in a more immature stage.
Following loss of myelin with cuprizone, the mice that lacked PTPRZ had more myelin repair than the normal mice. The researchers also found that a protein called pleiotrophin (PTN), seemed to be associated with remyelination in the mouse brains, suggesting that it may inactivate PTPRZ. When studied in vitro (in a dish), oligodendrocytes treated with PTN turned into a form that creates new myelin.
Overall, the study suggests that pleiotrophin is secreted by nerve cells when they are damaged and lose myelin, and pleiotrophin then inhibits PTPRZ. This allows oligodendrocytes to create new myelin.
The new understanding of how myelin is formed could provide the basis for new MS treatments, for example, drugs that inhibit PTPRZ or that increase pleiotrophin might be used in the future. Of course, much more research is needed and the investigators will need to find new compounds that act on PTPRZ.
According to Noda “This achievement was made possible by establishing oligodendrocyte precursor cell lines. Pleiotrophin is an endogenous PTPRZ inhibitor, but if synthetic PTPRZ inhibitors were obtained, then effective treatments for multiple sclerosis should become possible. We are currently directing our research in that direction.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (07/09/15)
Women with multiple sclerosis (MS) who intended to breastfeed their infants exclusively for two months had a lower risk of relapse during the first six months after giving birth compared with women who did not breastfeed exclusively , according to an article published online by JAMA Neurology.
About 20 percent to 30 percent of women with MS experience a relapse within the first three to four months after giving birth and there are no interventions for effective prevention of postpartum relapse. The effect of exclusive breastfeeding on postpartum risk of MS relapse is controversial with conflicting study results.
Kerstin Hellwig, M.D., of Ruhr-University Bochum, Germany, and coauthors analyzed data from 201 pregnant women with MS collected from 2008 to June 2012 with one-year follow-up postpartum in the nationwide German MS and pregnancy registry. Exclusive breastfeeding was defined as no regular replacement of breastfeeding meals with supplemental feedings for at least two months compared with nonexclusive breastfeeding, which was partial or no breastfeeding.
Of the 201 women, 120 (59.7 percent) intended to breastfeed exclusively for at least two months, 42 women (20.9 percent) combined breastfeeding with supplemental feedings within the first two months after giving birth, and 39 women (19.4 percent) did not breastfeed. Most women [178 (88.6 percent)] had used disease-modifying therapy (DMT) agents before pregnancy.
The authors report that 31 women (38.3 percent) who did not breastfeed exclusively had MS relapse within the first six months postpartum compared with 29 women (24.2 percent) who intended to breastfeed exclusively for at least two months.
The authors note the effect of exclusive breastfeeding "seems to be plausible" since disease activity returned in the second half of the postpartum year in exclusively breastfeeding women, corresponding to the introduction of supplemental feedings and the return of menstruation. The introduction of regular formula feedings or solid food to an infant leads to a change in a woman's hormonal status resulting in the return to ovulation.
The authors note the main limitation of their study was the selection bias inherent to voluntary registries and reflected in the high proportion of women receiving disease modifying treatments.
Source: Science Newsline © Newsline Foundation 2015 (01/09/15)