MS news and research
This page documents breaking multiple sclerosis news and research stories as they occur during the month.
For news and research for the previous 12 months please use the links on the menu on the left.
The news stories are taken from external sources and as such, MS-UK does not verify, endorse or accept responsibility for their content.
Some of these pages have been written for medical professionals and this can be reflected in the complexity of language and content. If you have any issues relating to the topics here, please call one of our advisors on 0800 7830 518.
AbbVie, Biogen to file MS drug next year(16/09/2014)
Phase-III results of the AbbVie-Biogen Idec experimental multiple sclerosis shot Zinbryta (daclizumab) indicate the drug bests Biogen's injectable Avonex (interferon beta-1a) on some measures among relapse-remitting MS patients. The companies released the full results at the Sixth Triennial Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis last week. The clinical trial of more than 1,800 patients showed Zinbryta patients had “significantly improved key measures of multiple sclerosis disease activity,” including a 45% reduction in relapses compared to Avonex patients and fewer new brain lesions. Researchers found that 73% of Zinbryta patients were relapse-free after 96 weeks of therapy, compared to Avonex patients, of whom 59% were relapse-free within the same timeframe.
Jefferies analyst Thomas Wei wrote in a Monday research note that results put the AbbVie-Biogen Idec contender in the same efficacy space as Novartis's oral Gilenya (fingolimod) and Biogen's Tysabri shot (natalizumab), even though patients had a slightly higher relapse rate on Zinbryta than patients in Gilenya trials.
Wei also noted that Zinbryta results showed a statistically significant impact on Paced Auditory Serial Addition Test scores which measure cognitive functions that are typically affected by the disease, whereas Gilenya offered what Wei called a numerical improvement.
Side effects included higher rates of skin reactions among Zinbryta patients than among Avonex patients, which AbbVie, Biogen and Wei considered consistent with the MS population as a whole, but Leerink analyst Joseph Schwartz wrote in a Thursday research note that a key opinion leader was bothered by the reaction.
An additional MS therapy may not enhance the finances of Biogen's MS portfolio: Jefferies analyst Thomas Wei said the 50-50 split with AbbVie could have a negative earnings impact if it takes away from sales of other Biogen MS products. Jefferies's Jeffrey Holford noted in his Monday assessment that Biogen's Tecfidera is also tussling with Biogen and non-Biogen MS drugs, and writes that the twice-daily oral is gaining new prescriptions at the expense of treatments including Biogen's Avonex and Teva's Copaxone, while also fighting for prescriptions against Gilenya and Sanofi's Aubagio (teriflunomide.)
AbbVie and Biogen Idec plan to file the drug with the FDA in the first half of next year.
During the 30th Congress of the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS) last week in Boston, Teva Pharmaceutical Industries Ltd. (NYSE:TEVA), together with Active Biotech (NASDAQ OMX NORDIC:ACTI), presented new follow-up data evaluating the clinical safety of laquinimod in patients with relapsing-remitting multiple sclerosis (RRMS) who were treated with laquinimod in Phase II, Phase III, and open-label extension studies for two or more years.
Teva Pharmaceutical Industries Ltd. (NYSE:TEVA), based in Israel, is the worldwide leading generic drug manufacturer, with a clinical focus on central nervous system (CNS) conditions, including pain, respiratory, oncology, and women’s health therapeutic areas as well as biologics. Active Biotech AB (NASDAQ OMX NORDIC:ACTI), located in Sweden, is a biotechnology company with focus on autoimmune/inflammatory diseases and cancer. Active is currently testing the laquinimod therapy, which is given orally, has immunomodulatory properties, and is used for the treatment of multiple sclerosis (MS).
“These data may be important as they further support the clinical safety profile of laquinimod,” said Michael Hayden, M.D., Ph.D., President of Global R&D and Chief Scientific Officer at Teva Pharmaceutical Industries, Ltd. “We believe laquinimod may have the potential to help physicians address certain gaps within the MS treatment paradigm as a potential therapeutic option when considering the benefits and risks in a longer-term setting.” added Michael Hayden.
The global Phase III clinical development program for the evaluation of laquinimod in MS includes 3 trial studies, ALLEGRO and BRAVO, which are testing one oral dose, 0.6 mg, and a third, named CONCERTO, which is evaluating two doses of the compound, 0.6mg and 1.2mg, per day. In the ALLEGRO and BRAVO trials, adverse reactions (AE) included headache, abdominal pain, back and neck pain, appendicitis, and mild, asymptomatic laboratory abnormalities, including liver enzyme elevations, like alanine aminotransferase (ALT), hematological changes, and elevation of C-reactive protein (CRP) or fibrinogen levels. The CONCERTO trial enrolled 2,100 patients with duration of 24 months. The primary outcome of this trial will be the measurement of disability progression of the patients using the Kurtzke Expanded Disability Status Scale (EDSS).
In the pooled safety analysis, rates of adverse and serious events were lower in the open-label extensions when compared with the core studies. Moreover, during these extensions, less than three percent of patients stopped the treatment due to AEs. Additionally, patients exposed to at least two years of laquinimod had lower changes in ALT experimental values (1.18% reached >3x upper limit of normal (ULN) ALT vs. 4.72% for laquinimod and 2.6% for placebo [inactive compound]) during the core study. In the double-blind phase and open-label extensions of the Phase II LAQ/5063 and the Phase III ALLEGRO and BRAVO trials, the safety analysis included patients exposed to laquinimod, 0.6 mg per day, for two or more years (n=1009), with a mean exposure of 3.7 (±1.0) years.
“In this pooled analysis, laquinimod has shown to be safe for patients taking the treatment for two or more years, which supports the safety profile of laquinimod when used in a longer-term setting,” said Professor Giancarlo Comi, Director of the Department of Neurology and Institute of Experimental Neurology at the San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy. “In a separate analysis, we were pleased to see that when used in a longer-term setting, laquinimod continued to show a favorable effect on relapses and confirmed disability progression, maintaining the benefits previously seen in Phase III studies.” added Professor Giancarlo Comi.
In addition to the MS clinical studies, laquinimod will be assessed in terms of efficacy, safety, and tolerability for other neurodegenerative diseases including Huntington’s disease.
The fatigue many people with multiple sclerosis (MS) experience may actually be a sign of an undiagnosed sleep disorder, according to a new study.
Researchers found that sleep disorders, which are more common among people with MS, are often left undiagnosed and untreated. Left untreated, sleep disorders could affect the progression of the disease, as well as affect people's overall well-being, the study authors cautioned.
"Sleep disorder frequency, sleep patterns and complaints of excessive daytime sleepiness suggest that sleep problems may be a hidden epidemic in the MS population, separate from MS fatigue," said Steven Brass, associate clinical professor and director of the Neurology Sleep Clinical Program and co-medical director of the UC Davis Sleep Medicine Laboratory in a university news release.
MS is an inflammatory disease affecting the white matter and spinal cord. Although the cause of MS is unclear, it is thought to be an autoimmune condition, according to the researchers. Symptoms include vision loss, vertigo, weakness and numbness. Fatigue is also a key symptom of MS. The study, published online on Sept. 12 in the Journal of Clinical Sleep Medicine, involved almost 2,400 people diagnosed with MS. Most of the study participants were women, and most were white. The mean age was 54 years.
The participants were asked to complete a survey that included questions about their sleep history, daytime sleepiness, insomnia and restless legs syndrome. Nearly 52 percent of the participants needed more than 30 minutes to fall asleep at night. Almost 11 percent needed medication to help them fall asleep.
The researchers found that more than 70 percent of these patients had at least one sleep disorder. Nearly 38 percent of those surveyed were diagnosed with obstructive sleep apnea, almost 32 percent had moderate to severe insomnia and around 37 percent had restless legs syndrome.
However, most of the patients with a sleep disorder had not been diagnosed, the study revealed. In fact, only about 4 percent of those with obstructive sleep apnea had been diagnosed by a doctor.
"A large percentage of MS subjects in our study are sleep deprived and screened positive for one or more sleep disorders," said Brass. "The vast majority of these sleep disorders are potentially undiagnosed and untreated. This work suggests that patients with MS may have sleep disorders requiring independent diagnosis and management."
Source: HealthDay 12/09/2014
A well-tolerated oral medication for some forms of multiple sclerosis (DMF) appears to provide sustained benefit for patients, and favourable outcomes were seen on a composite outcome measure over a five-year period, according to a study presented at the 2014 Joint ACTRIMS-ECTRIMS Meeting, held in Boston, MA.
Gavin Giovannoni, MD, of Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK presented five-year findings from this follow-on outcomes study of dimethyl fumarate (DMF), an oral disease-modifying agent approved in the US to treat relapsing-remitting multiple sclerosis (RRMS).
An increasingly common measure of treatment efficacy for patients with MS is no evident disease activity, or NEDA. It is a composite measure consisting of relapse rate, disability outcomes, and neuroimaging findings. Change over time can be captured in tracking NEDA outcomes when data are broken out by yearly interval and subjects are re-baselined at each year. Giovannoni reported long-term NEDA for patients with RRMS who either continued DMF or switched to the drug to participate in the ENDORSE study. ENDORSE, the study reported here, is an extension of the DEFINE and CONFIRM studies, which compared DMF to placebo and to glatiramer acetate (GA), respectively. .
In transitioning patients to the extension study for years 3-5, patients who had been on placebo or GA were re-randomized to DMF BID or TID. The DMF BID subset was assessed for this study, since this is the dosage of DMF that was eventually approved for the treatment of RRMS. The group was further narrowed to include only those patients who had both clinical and magnetic resonance imaging (MRI) data. At the beginning of ENDORSE, 211 patients were continued on BID DMF, while 104 were transitioned from placebo to BID DMF and 48 switched from GA to BID DMF. Delayed-release DMF, also known as gastro-resistant DMF, was used for the ENDORSE study. Demographics, number of relapses in prior year and EDSS scores were similar across groups, while mean number of gadolinium (GD) enhancing lesions was slightly higher for the DMF group, at 2.1 vs. 1.4 each for the other two groups.
Breaking out findings into yearly assessment of absence of measured clinical activity, absence of measured MRI activity, and NEDA, Giovannoni reported that both the placebo and GA groups showed improvement when transitioning to DMF. All three subgroups showed sustained improvement by the end of year five, with 86% of the DMF/DMF group, 90.1% of the placebo/DMF group, and 84.5% of the GA/DMF group having absence of measured clinical activity by the end of year five. These figures showed modest improvement over clinical activity just before enrollment in ENDORSE, when 81.0%, 71.1%, and 77.6% showed no clinical activity, respectively.
No measured MRI activity was seen by the end of year five in 62.1% of the DMF/DMF group; 62.9% had been free of MRI activity at the end of year two. For the placebo group, 66.1% were free of MRI abnormalities at the end of ENDORSE data collection, while only 33.7% had no MRI activity at the end of year two. The GA acetate group improved, similarly, with 56.7% of patients having no measured MRI activity at the end of year five, in contrast with 40.9% at enrollment in ENDORSE.
Finally, the composite measure of NEDA showed that 42.5% of BID/BID enrollees had NEDA by year five, as did 43.2% of placebo/BID patients and 31.6% of GA/BID patients. By contrast, NEDA was seen in 50.2% of BID/BID patients, 43.2% of placebo/BID patients, and 31.6% of GA/BID patients by the end of year two.
In comments during his presentation and in answering questions afterward, Giovannoni noted that study subjects who had been on DMF for the entire five-year period had higher NEDA scores over that time span, faring better overall than the patients who had switched to DMF after a period of time on placebo or GA. Individuals who only began DMF at the beginning of ENDORSE, however, did show improvement on the new regime after re-baselining. Informal discussion after the presentation highlighted the relatively small numbers of subjects enrolled in various arms of the study, which Giovannoni feels may have accounted for some of the data showing less robust improvement in NEDA scores.
Source: HealthCare Professionals Network 13/09/14
The thinning of the retina that occurs during the course of multiple sclerosis (MS) closely parallels brain atrophy and may be used to measure neurodegeneration, a new study has shown.
Presenting the data here at MSBoston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting, Shiv Saidha, MD, Johns Hopkins Hospital, Baltimore, Maryland, explained that previous studies had correlated retinal thinning with global disability and brain atrophy, but these studies were primarily cross-sectional in design.
"Our study is groundbreaking in that it is the first ever longitudinal study to look at how retinal changes measured by optical coherence tomography (OCT) track with MRI measures of brain atrophy," he said. "These results could have far-reaching implications for the field of neurodegeneration."
"We showed clearly that the degree of retinal layer thinning predicts the loss of brain tissue. Patients who lost the most neurons in the retina had the highest amount of brain loss on MRI."
He added: "It was particularly effective in patients with progressive MS, but it can be used from the very beginning to identify which patients are deteriorating the fastest."
The MS field has suffered from a lack of tools to track neurodegeneration, and much work is underway to identify such markers, Dr. Saidha added. "Our data shows that measuring changes in the retina with OCT is one of the most promising techniques for this purpose."
"It is easy to do — it takes just 5 minutes to assay the retina," he commented to Medscape Medical News. "It is cheap and easily reproducible. In my view, it is very encouraging."
Validation for Use in Clinical Trials
These opinions were echoed by the chair of the Young Investigators session at which Dr. Saidha presented the study, Patrick Vermersch, MD, Centre Hospitalier Régional Universitaire de Lille, France.
"This study is really interesting," he told Medscape Medical News. "This methodology adds complementary information to explain the neurodegenerative process in MS. Measuring retinal thinning with OCT is much easier than trying to assess brain atrophy with MRI. It is already being used as a marker of treatment response in therapeutic trials, but this study gives validation that this is an appropriate marker to measure."
Dr. Vermersch suggested that OCT may not be as sensitive as measuring brain atrophy with MRI, but it is far more convenient. "I would think MRI will be superior, but it is not widely available," he added. "It is not possible to measure brain atrophy in routine clinical practice — the specific software is only available in specialist centers for research use at present. But OCT is widely available and easy to use."
For the study, 108 MS patients underwent OCT every 6 months (average follow-up duration, 42 months) and annual MRI (3T) of the brain (average follow-up duration, 39 months). Patients with optic neuritis during the study were excluded. Individual-specific rates of change in retinal and brain measures were correlated after adjustment for age, sex, disease duration, and optic neuritis history.
Results showed that the thickness of the ganglion cell layer plus inner plexiform layer of the retina together (GCIP) had the best correlation to whole brain atrophy, with a correlation coefficient of 0.449. GCIP loss was also correlated to atrophy in gray matter (r = 0.371), white matter (r = 0.285), and thalamic (r = 0.379) regions of the brain over time.
Best in Secondary Progressive Disease
The correlation between GCIP and brain atrophy rates was stronger in secondary progressive MS (r = 0.730) and primary progressive MS (r = 0.542) than in relapsing-remitting MS (r = 0.328).
"Although the association between GCIP and brain atrophy in relapsing-remitting MS is impressive, the association in progressive MS, particularly secondary progressive MS, appears to be exceptional," Dr. Saidha stated.
The relationship between GCIP and brain atrophy was affected by history of optic neuritis, which reduced the strength of the correlation, especially in the relapsing-remitting population.
Dr. Saidha reported that for every yearly change of 1 micron in GCIP thickness there was a 0.45% yearly brain loss in eyes without a history of optic neuritis. GCIP atrophy also mirrored lesion accumulation in MS, although this was not as strong as the relationship with brain atrophy.
"Our findings confirm the utility of OCT for tracking subclinical as well as clinical disease progression in MS and establish a role for OCT in clinical trials for the objective investigation of neuroprotection," Dr. Saidha concluded.
Primary Source: MSBoston 2014: 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS). Abstract Y12.2. Presented September 10, 2014.
Source: Medscape Multispeciality © 1994-2014 by WebMD LLC (12/09/14)
A new study suggests no cognitive disadvantage in the long term for patients with multiple sclerosis (MS) that began in childhood vs those with adult-onset disease.
Researchers are reporting that overall, cognitive outcomes were similar between the groups and that there were actually fewer patients in the paediatric-onset group, matched with adult-onset patients for age and education, who were classified as cognitively impaired. However, the difference between groups was not statistically significant.
"Since disease onset in a period of active brain growth and maturation may render pediatric-onset subjects more vulnerable to cognitive issues, our findings suggest good compensatory/recovery abilities in these subjects, possibly related with enhanced brain plasticity in early life," the researchers, with lead author Bahia Hakiki, from the University of Florence, Italy, concluded.
Dr. Hakiki presented their findings here at MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS).
Paediatric-onset MS represents 3% to 5% of the overall MS population and "poses unique diagnostic and therapeutic challenges," she noted. Compared with patients developing adult-onset disease, pediatric patients have relapsing-remitting disease course at onset in more than 90% of cases, have higher clinical and MRI disease activity, and have a slower rate of disability accumulation, although disability is still seen at a younger age.
Cognitive issues are "particularly relevant" in this population, she added, because disease occurs during key periods of brain growth, active primary myelination, maturation of neural networks, and key academic training years. "But on the other hand, brain plasticity and recovery may be more efficient in this group," Dr. Hakiki said. "For this reason, final outcome of cognitive performance can be evaluated only in the long term."
Previous studies suggest a prevalence of cognitive impairment in paediatric-onset disease of 30% to 50%, with a neuropsychological pattern similar to that seen in adult-onset MS, including particular involvement of attention, information-processing speed, learning and memory, executive function, and visuospatial abilities, she noted. "Moreover, it has some peculiar aspects of cognitive impairment," she said, with involvement of linguistic skills, which is spared in adult-onset MS, and sometimes an effect on genera intelligence.
The aim of this study, then, was to determine whether the cognitive effects in adulthood are worse among paediatric-onset vs adult-onset cases and, if so, to what extent. They also looked to see whether they could identify any predictors of compensatory abilities in the paediatric-onset patients.
To do this, they compared cognitive performance between 2 groups of adults with MS: 1 that had paediatric-onset disease and 1 with adult-onset disease. Patients were matched for age, education, relapsing-remitting disease course, and scores on the Expanded Disability Status Scale. Patients with a history of conditions that would be expected to interfere with cognition, such as head trauma, learning disability, or drug and alcohol abuse were excluded.
All participants underwent neuropsychological assessment using Rao's Brief Repeatable Battery (which assesses learning memory, visuospatial abilities, attention and information-processing speed, and verbal fluency) and the Stroop test (which gauges executive function). Depression was also assessed by using the Montgomery-Asberg Depression Rating Scale and fatigue by using the Fatigue Severity Scale. Significant cognitive impairment was defined as failure on more than 2 cognitive tests.
Ongoing analyses include basal IQ, assessment of leisure activities, and parental education, Dr. Hakiki noted, which should allow the investigators to estimate cognitive reserve in the participants.
In addition to cognitive testing, conventional MRI was done, assessing T1 and T2 lesion volume as well as brain volume, white matter volume, and cortical volume. Resting-state functional MRI is ongoing in these groups.
For this analysis, the authors compared 30 adult-onset patients (9 men and 21 women) with 14 paediatric-onset patients (8 men and 6 women), with an average age of 25 and 27 years, respectively. As expected, the duration of disease was longer in the paediatric-onset patients than the adult-onset patients: 9.8 years vs 3.7 years. They were well matched in terms of EDSS scores, disease course, and use of disease-modifying therapies, she noted.
Less Cognitive Impairment
No difference was found between the groups in terms of mean scores on the neuropsychological tests or in the number of tests failed, Dr. Hakiki reported. Interestingly, more patients in the adult-onset group than the paediatric-onset group met criteria for cognitive impairment: 27% vs 14%. No differences were found in measures of fatigue or depression.
The cognitive profile across tests was similar between the 2 groups, she said, "showing a prominent involvement of tests exploring information processing speed, followed by tests exploring executive function and memory."
In a subset of 22 patients who underwent MRI (11 pediatric and 11 adult-onset patients), the paediatric-onset patients showed a nonsignificant trend toward higher white-matter lesion load, but no differences were seen between the groups in terms of brain volumes.
"The comparable brain volumes, despite a longer disease duration and tendency to accumulate more lesions, may suggest a greater repair capability in these patients," Dr. Hakiki concluded.
Going forward, they hope to extend the study sample, complete the assessments of cognitive reserve as well as MRI analysis, and then integrate the cognitive and MRI data, she said.
Brenda L. Banwell, MD, chief of neurology at the Children's Hospital of Philadelphia, Pennsylvania, who comoderated the Young Investigators session where these results were presented, pointed out that the age at onset for the paediatric-onset patients was 15.6 ± 2.1 years.
"The resiliency to cognitive impairment may be very different of course in patients who start much younger," Dr. Banwell said. "Obviously you can't address that in this cohort, and you only had 14% cognitive impairment, which is what about half of studies that included younger kids have shown. Are you going to repeat this now with younger-onset patients?"
Dr. Hakiki noted they are planning to include younger-onset patients in the extended study sample to address this question.
Dr. Banwell told Medscape Medical News that both groups were relatively intact even though the paediatric-onset patients had a longer disease duration.
"The low proportion of impaired patients limits the ability to correlate with imaging," she noted. "Further work in a larger group whose MS onset occurred at a younger age — especially prepuberty — would be of great value."
Primary Source: MS Boston 2014: 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS). Abstract YI2.3. Presented September 10, 2014.
Source: Medscape Multispeciality © 1994-2014 by WebMD LLC (12/09/14)
Whole-brain measures of myelin water fraction (MWF) -- reflecting the amount of myelin present in brain tissue -- correlated significantly with disease duration and disability levels in multiple sclerosis, supporting a role for MWF in patient management and as an outcome in clinical trials, a researcher said here.
In a cross-sectional study of 141 MS patients and 10 neurologically healthy controls, the "skew" of one of two peaks seen in the distribution of MWF across the brain, including normal-appearing white matter as well in MS-type lesions, was associated with Expanded Disability Status Scale (EDSS) score (P=0.000039) and with the number of years since symptom onset (P=0.012), said Elizabeth Monohan, of Weill Cornell Medical College in New York City.
"To date, our study is the first to demonstrate an approach to modeling white matter myelin water fraction to explore clinical variables that may be driving myelin content," she said at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting, held jointly this year with its North American counterpart.
"These observations promote the use of myelin water fraction as a biomarker for myelin," she added, noting that the relationship between MWF on the one hand and EDSS and disease duration on the other suggests that "myelin loss is accumulated during the disease and perhaps contributes to the progressive nature of MS."
Demyelination is the chief pathology in MS and is believed to be the driving force behind the physical disabilities that mark the disease in its later stages. Nerve fibers are sheathed in a protective layer of proteins dominated by myelin; its progressive loss leaves nerve axons vulnerable to various insults such that eventually they break down, leading to loss of nerve function.
However, this process has been impossible to witness or measure directly in human patients. Recently, MWF -- measurable with MRI scans as the amount of water within myelin versus the total amount of water in the tissue scanned -- has emerged as a quantitative marker of myelin that can be assessed noninvasively in living patients.
Up till now, though, its clinical applicability has been uncertain, Monohan explained, because it was unclear whether focusing on MWF in lesioned areas was sufficient and also because the scans took a long time to perform and data analysis was difficult.
She said her group had developed a more practical approach to the scans that cut the image acquisition time to just 10 minutes for the whole brain. Moreover, she and her colleagues determined that scanning the whole brain was the right way to go, because there was no solid evidence to indicate that the clinically relevant demyelination occurs only in lesions.
The whole-brain MWF measurement, Monohan said, provides an "unbiased approach" for studying myelin dynamics.
An important finding in the study was that patients showed a "bimodal" distribution in histograms of MWF values -- a small spike in relatively low values and another larger spike in mid-range values. Monohan said that 94% of the patients showed this type of pattern, compared with just one of the 10 controls.
It was the shape of this spike in low values -- primarily the skew, but also its width -- that was most strongly correlated with EDSS and disease duration, she reported. The shape of the larger mid-value spike was associated with EDSS score but not disease duration.
Monohan said her group is pursuing additional studies to look at a broader patient population, with a wider range of EDSS scores and disease durations. Another goal is to examine MWF in patients undergoing treatment with current MS drugs.
Also, longitudinal studies to track within-patient changes in MWF over time will be necessary to determine how it may correlate with lesion evolution and, importantly, disease progression.
The study was funded by the National Multiple Sclerosis Society and the National Institutes of Health.
Study investigators had relationships with Biogen Idec, Teva, Questcor, Genzyme, EMD Serono, Novartis, and Acorda.
Primary source: ECTRIMS-ACTRIMS
Source reference: Monohan E, et al "Clinical disease burden predicts myelin water fraction in multiple sclerosis" ECTRIMS-ACTRIMS 2014; Abstract YI1.3.
Source: Medpage Today © 2014 MedPage Today, LLC. (12/09/14)
There is a clear subset of pediatric patients with demyelinating disease who have substantial damage to the nerve layer in the retina but nevertheless have no vision loss, a new study shows.
"Understanding how this subset of patients recover functionally after optic nerve damage could lead to great insight into best acute treatment options and a better understanding of brain plasticity and neural networking," lead author Samuel Hughes, BS, UT Southwestern Medical Center, Dallas, Texas, concluded.
"We need to analyse other variables in these children, including age, sex, time to acute treatment, and type of treatment to see if we can shed light on how this is occurring."
He presented their findings here at MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting.
"This is a really crazy cohort of kids that no one has identified before who can see normally but from looking at their retina they should be blind," Hughes said.
"Maybe there is some kind of mechanism that children have but adults don't to compensate for the loss of nerve fibres in the retina," he speculated. "We need to understand better what it is about these children that helps them recover functionality. Something could be happening in the visual cortex of the brain causing it to rewire."
He added that this could have implications for understanding neural networking and finding treatments for the adult population with demyelinating disease. "If we could pinpoint what is happening in the brains of these children we may be able to figure out some functional stimulation to enhance that process."
Cochair of the session at which the study was presented, Patrick Vermersch, MD, PhD, Centre Hospitalier Régional Universitaire de Lille, France, called this an "interesting observation. It certainly appears that the optic nerve in some children is more resilient than in adults. We need to learn why this is the case," he told Medscape Medical News.
As background, Hughes noted that in adults visual acuity (especially low contrast) correlates to retinal nerve fiber layer thinning as measured by optical coherence tomography (OCT), and a threshold of 75 microns predicts persistent visual dysfunction. But these measures have not been well established in children.
For the current study, OCT data and corresponding visual acuities were obtained from a total of 378 eyes of children with demyelinating disease, including multiple sclerosis, acute disseminated encephalomyelitis, or idiopathic optic neuritis.
Results showed that while there was a relationship between the thickness of the retinal nerve layer and visual acuity in most patients, a small subset of 9 eyes had a very thin retinal nerve layer (55 to 59 microns) but the patients had normal high and low visual acuity.
Hughes noted that it is important to validate the normative data in the pediatric population.
"OCT is well validated in adults. It is a ubiquitous tool for understanding optic nerve damage and is starting to be used as a proxy for disease progression. It is being used in the pediatric population but our data begs the question that we may need different parameters in children."
MS Boston 2014: 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) Meeting. Abstract Y12.4 Presented September 10, 2014.
Source: Medscape Multispeciality © 1994-2014 by WebMD LLC (12/09/14)
Biogen Idec today announced new data from the second year of its Phase 3 ADVANCE clinical trial that show the positive treatment effects of Plegridy™ (peginterferon beta-1a) were maintained in people with relapsing forms of multiple sclerosis (RMS) beyond the first year of the study. These results were presented at the sixth Triennial Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS) in Boston.
“These new, two-year data from ADVANCE further support the compelling efficacy and safety of Plegridy, providing physicians and patients with additional confidence in the benefits of using Plegridy to treat this chronic disease,” said Gilmore O’Neill, vice president, Multiple Sclerosis Research and Development at Biogen Idec.
Efficacy and Safety of Plegridy Maintained Over Two Years
Post-hoc analyses from the two-year, Phase 3 ADVANCE clinical trial confirm that Plegridy’s positive effects on reducing disease activity and disability progression were maintained in year two of the study. A significantly higher proportion of patients taking Plegridy during both years of the study experienced no evidence of disease activity (NEDA) – defined as the absence of clinical and MRI disease activity over two years of treatment – compared to those who switched to Plegridy from placebo. Also, those treated with Plegridy for both years of the study had significant reductions in the risk of 24-week confirmed disability progression compared to patients treated with placebo during the first year.
In addition, new data from the second year of ADVANCE show that patients who took Plegridy throughout the study experienced statistically significant improvements in clinical and MRI outcomes – including annualized relapse rate (ARR), risk of relapse, risk of 24-week confirmed disability progression, and number of brain lesions – when compared to those who switched to Plegridy after taking placebo for the first year. This new data also showed that the safety profile of Plegridy was consistent between years one and two of the study.
“The ADVANCE data suggest that treatment with Plegridy offers benefits in reductions in relapses, confirmed disability progression and brain lesions over the course of two years,” said Douglas Arnold, M.D., professor, Montreal Neurological Institute, McGill University. “Results from the second year of ADVANCE also confirm the positive safety and tolerability profiles of Plegridy seen in year one, which is very encouraging.”
Source: MarketWatch ©2014 MarketWatch, Inc (11/09/14)
New study finds a generic version of Copaxone to be just as effective, safe
A new study on the first generic medication for Multiple Sclerosis is showing promising results when compared to the widely-used name brand medication, Copaxone.
"The study was positive. It showed that the generic version of glatiramer acetate, Copaxone, was equivalent," said Cleveland Clinic neurologist Dr. Jeff Cohen, a principal investigator in this study.
Cohen and his team of researchers tested the effects of generic glatiramer acetate on nearly 800 people. MRI was used to determine if the generic version was comparable at inhibiting brain-lesion activity. Researchers also checked the generic's effectiveness at controlling relapses and other disability changes.
Cohen says the generic is not only comparable but it is equally safe. He says the next step will be to complete the extended follow-up on the safety and efficacy of the drug, but added the initial results are encouraging.
"So, we think these are very interesting results and hopefully will lead to the availability of generic versions of some of the multiple sclerosis medications, which could lead to significant cost-savings," Cohen said.
After the next round of tests, Cohen says the medication would then be considered for approval from the Food and Drug Administration. He hopes the generic version will be available sometime next year.
Source: News4Jax Copyright 2014 by News4Jax.com (11/09/14)
Sanofi rare disease unit Genzyme hopes to become a leader in the multiple sclerosis (MS) field with the help of new products developed in-house but also through acquisitions, senior Genzyme executives told Reuters.
The Cambridge, Massachusetts company is confident in the commercial success of its two MS drugs Lemtrada and Aubagio and is "very active" in its hunt for external growth, Bill Sibold, the head of Genzyme's MS franchise, told Reuters.
He declined to comment on potential targets but said Genzyme was looking to snap up truly innovative products, was regularly talking to other companies and constantly weighing its options.
Asked if Genzyme had a budget for acquisitions or if "the sky's the limit", Sibold laughed and simply replied that it helped to be a part of Sanofi - a group with deep pockets: "If the opportunity is the right opportunity, we'll evaluate it... We're well resourced to execute our strategy."
Pricing pressures from cash-strapped governments seeking to restrict healthcare spending and tough competition from generics have prompted drugmakers worldwide to reshuffle their businesses and triggered a wave of mergers and acquisitions.
Sanofi bought Genzyme, a U.S. biotech firm, for $20.1 billion in 2011 as part of a broader revamp of its drug portfolio. The unit posted a 25 percent jump in sales in the first half of the year, and is one of the core emerging businesses Sanofi is betting on to shake off the impact of patent losses on older drugs such as its blood thinner Plavix.
At the heart of the Genzyme takeover stood its injectable drug Lemtrada, designed to treat relapsing remitting multiple sclerosis, the most common form of the disease, in a market dominated by rivals Biogen Idec, Novartis and Teva Pharmaceutical Industries.
Lemtrada is already sold in Europe but has yet to be approved in the United States, where experts have raised questions about its safety and the quality of clinical studies.
Analysts slashed their sales forecasts for the drug after the U.S. Food and Drug administration rejected Lemtrada's application last December. Sanofi resubmitted an application earlier this year and expects FDA action in the fourth quarter.
"I'm confident in the U.S. approval and I'm confident in how the product will perform and be utilised... The efficacy is just too good," said Mike Panzara, therapeutic area head for Genzyme's MS and neurology program.
Multiple sclerosis is a chronic, autoimmune condition which affects more than 2 million people worldwide and up to 500,000 in the U.S. It attacks the central nervous system and can cause muscle weakness, pain and cognitive difficulties.
Lemtrada is given in two courses via an intravenous drip and is designed to reprogramme the immune system, but in so doing can make the body more vulnerable to other diseases.
The market is increasingly moving away from injectable treatments in favour of pills such as Novartis' Gilenya and Biogen Idec's Tecfidera, but Genzyme is hopeful Lemtrada's ability to durably reduce the risk of relapse of the disease will win it a slice of the market.
Genzyme is presenting this week before the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS) a raft of clinical data for Lemtrada, which Panzara said supports the drug's favourable benefit-risk profile.
"The risks are those that we previously described... But without an increase in risk the longer you follow the patient," he said, stressing that 30 countries had already approved the drug and that it had support from patients and physicians alike.
The ECTRIMS annual meeting will also feature new data on Aubagio, an oral treatment already approved in the U.S and Europe and for which analysts are much more upbeat.
Analysts on average expect Aubagio to hit peak sales of $1.2 billion by 2018, compared with $437 million for Lemtrada, according to forecasts compiled by Thomson Reuters Cortellis.
Sibold declined to comment on the forecasts, but noted that analysts had been pleasantly surprised by Aubagio, and suggested they may also now be underestimating Lemtrada.
"We think that the potential of both products, Lemtrada and Aubagio, is really enormous. Each of them can be a blockbuster," he said.
Source: Reuters © Thomson Reuters 2014 (11/09/14)
Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: Boosting autoimmunity to fight-off chronic neuroinflammation.
Schwartz M, Baruch K.
Immune cell infiltration to the brain's territory was considered for decades to reflect a pathological process in which immune cells attack the central nervous system (CNS); such a process is observed in the inflammatory autoimmune disease, multiple sclerosis (MS).
As neuroinflammatory processes within the CNS parenchyma are also common to other CNS pathologies, regardless of their etiology, including neurodegenerative disorders such as Alzheimer's disease (AD) and Amyotrophic lateral sclerosis (ALS), these pathologies have often been compared to MS, a disease that benefits from immunosuppressive therapy.
Yet, over the last decade, it became clear that autoimmunity has a bright side, and that it plays a pivotal role in CNS repair following damage. Specifically, autoimmune T cells were found to facilitate CNS healing processes, such as in the case of sterile mechanical injuries to the brain or the spinal cord, mental stress, or biochemical insults. Even more intriguingly, autoimmune T cells were found to be involved in supporting fundamental processes of brain functional integrity, such as in the maintenance of life-long brain plasticity, including spatial learning and memory, and neurogenesis.
Importantly, autoimmune T cells are part of a cellular network which, to operate efficiently and safely, requires tight regulation by other immune cell populations, such as regulatory T cells, which are indispensable for maintenance of immunological self-tolerance and homeostasis.
Here, we suggest that dysregulation of the balance between peripheral immune suppression, on one hand, and protective autoimmunity, on the other, is an underlying mechanism in the emergence and progression of the neuroinflammatory response associated with chronic neurodegenerative diseases and brain aging.
Mitigating chronic neuroinflammation under these conditions necessitates activation, rather than suppression, of the peripheral immune response directed against self.
Accordingly, we propose that fighting off acute and chronic neurodegenerative conditions requires breaking peripheral immune tolerance to CNS self-antigens, in order to boost protective autoimmunity. Nevertheless, the optimal approach to fine tune such immune response must be individually explored for each condition.
Source: J Autoimmun. 2014 Sep 5. pii: S0896-8411(14)00127-9. doi: 10.1016/j.jaut.2014.08.002 © 2014 Elsevier Ltd & Pubmed PMID: 25199710 (11/09/14)
People with multiple sclerosis (MS) lose myelin in the grey matter of their brains and the loss is closely correlated with the severity of the disease, according to a new magnetic resonance imaging (MRI) study. Researchers said the findings could have important applications in clinical trials and treatment monitoring. The study appears online in the journal Radiology.
Loss of myelin, the fatty protective sheath around nerve fibres, is a characteristic of MS, an inflammatory disease of the central nervous system that can lead to a variety of serious neurological symptoms and disability. MS is typically considered a disease of the brain's signal-conducting white matter, where myelin is most abundant, but myelin is also present in smaller amounts in grey matter, the brain's information processing center that is made up primarily of nerve cell bodies. Though the myelin content in grey matter is small, it is still extremely important to proper function, as it enables protection of thin nerve fibers connecting neighbouring areas of the brain cortex, according to Vasily L. Yarnykh, Ph.D., associate professor in the Department of Radiology at University of Washington in Seattle.
"The fact that MS patients lose myelin not only in white but also in grey matter has been proven by earlier post-mortem pathological studies," he said. "However, the clinical significance of the myelin loss, or demyelination, in grey matter has not been established because of the absence of appropriate imaging methods."
To learn more about associations between MS and demyelination in both white and grey matter, Dr. Yarnykh and colleagues used a refined MRI technique that provides information on the content of biological macromolecules - molecules present in tissues and composed of a large number of atoms, such as proteins, lipids and carbohydrates. The new method, known as macromolecular proton fraction (MPF) mapping, has been hampered in the past because of the length of time required for data collection, but improvements now allow much faster generation of whole-brain maps that reflect the macromolecular content in tissues.
"The method utilises a standard MRI scanner and doesn't require any special hardware-only some software modifications," Dr. Yarnykh said. "MPF mapping allows quantitative assessment of microscopic demyelination in brain tissues that look normal on clinical images, and is the only existing method able to evaluate the myelin content in grey matter."
The researchers looked at 30 MS patients, including 18 with relapsing-remitting MS (RRMS), the most common type of MS initially diagnosed, and 12 with the more advanced type of disease known as secondary progressive MS (SPMS). Fourteen healthy control participants were also included in the study. Each participant underwent MRI on a 3-Tesla imager, and the researchers reconstructed 3-D whole-brain MPF maps to look at normal-appearing white matter, grey matter and MS lesions. The researchers further compared the results of their imaging technique with clinical tests characterising neurological dysfunction in MS patients.
The results showed that MPF was significantly lower in both white and grey matter in RRMS patients compared with healthy controls, and was also significantly reduced in both normal-appearing brain tissues and lesions of SPMS patients compared to RRMS patients with the largest relative decrease in grey matter. MPF in brain tissues of MS patients significantly correlated with clinical disability and the strongest associations were found for grey matter.
"The major finding of the study is that the loss of myelin in grey matter caused by MS in its relative amount is comparable to or even larger than that in white matter," said Dr. Yarnykh. "Furthermore, grey matter demyelination is much more advanced in patients with secondary-progressive MS, and it is very strongly related to patients' disability. As such, we believe that information about grey matter myelin damage in MS is of primary clinical relevance."
The improved technique has potentially important applications for MS treatments targeted to protect and restore myelin.
"First, this method may provide an objective measure of the disease progression and treatment success in clinical trials," Dr. Yarnykh said. "And second, assessment of both grey and white matter damage with this method may become an individual patient management tool in the future."
Dr. Yarnykh and colleagues are currently conducting additional research on the new method with the support of the National Multiple Sclerosis Society and the National Institutes of Health.
"This study was done on the participants at a single point in time," he said. "Now we want to compare MS patients with control participants to see how myelin content will evolve over time. We further plan to extend our method to the spinal cord imaging and test whether the combined assessment of demyelination in the brain and spinal cord could better explain disability progression as compared to brain demyelination alone."
Source: News-Medical.Net Copyright 2000-2014 AZoM.com Limited (10/09/14)
New International Survey Finds MS Patients and Neurologists View Communication Positively, Yet Struggle to Discuss Key MS Symptoms.
– Neurologists Underestimate Patient Discomfort with Discussing More Typical Symptoms
– Patients Most Uncomfortable Engaging in Candid Dialogue about More Private Symptoms
– Patients and Physicians Not Always Aligned
Findings from an international survey show differences in the perceptions of people living with multiple sclerosis (MS) and neurologists when discussing MS symptoms, including those that are personal and sensitive. While the results generally suggest a positive assessment of current practice in MS, important gaps were identified that could potentially impact disease management and patient quality of life. These findings will be presented this week at the Sixth Triennial Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS) in Boston.
The survey, commissioned by Biogen Idec and conducted online by Harris Poll, was developed in partnership with the State of MS Consortium, an international steering committee of treating neurologists from five countries and representatives from patient advocacy groups. The survey involved MS patients and neurologists who treat the disease in Germany, Italy, Spain, the United Kingdom (UK) and United States (U.S.) and aimed to understand the current experiences of those living with and treating the disease, including communication between MS patients and their physicians.
“There are a variety of symptoms a person living with MS can experience, and as physicians we need to constantly evaluate the most effective strategies to address all of our patients’ needs,” said Mar Tintore, M.D., Ph.D., senior consultant neurologist, Neurology-Neuroimmunology Department, MS Centre of Catalonia, Hospital Vall d’Hebron, Barcelona, Spain. “This survey illustrates that while there is a high degree of satisfaction with overall physician-patient communication, disconnects between patients and physicians mean some symptoms could be under-managed.”
Despite Open Communication, Discomfort Remains in Discussing Typical Symptoms, Including Those That Are Private and Sensitive
More than eight in ten patients (83 percent) say they feel comfortable talking about their MS with their neurologists, noting their neurologist provides them with helpful information (81 percent). Moreover, 85 percent of patients characterise their neurologist as honest in setting their expectations for therapy success. Similarly, nearly all neurologists (96 percent) feel they have an open dialogue in which their patients can ask any question they want, and 90 percent indicate they have a good understanding of all aspects of their patients’ disease. Yet a divide exists specifically around communication about certain MS symptoms.
Neurologists tend to underestimate their patients’ discomfort talking about MS symptoms often associated with the disease, while overestimating patient discomfort discussing other, more private symptoms. Nearly one in five patients who experience MS symptoms report being uncomfortable speaking with their neurologist about their difficulty walking (19 percent), tremors (19 percent) and muscle spasms (18 percent), but only two to three percent of neurologists identify these symptoms as uncomfortable topics for their patients to discuss with them. Conversely, neurologists are in alignment with patients when identifying the most difficult topics for patients to discuss, and tend to expect a higher level of discomfort than what is expressed by patients. The sensitive symptoms that emerged as the most uncomfortable for patients to discuss were sexual difficulties (54 percent of patients, with 87 percent of neurologists perceiving this as being uncomfortable for patients) bladder or bowel problems (28 percent; 54 percent), mood swings (26 percent; 37 percent) and cognitive/memory issues (21 percent; 37 percent).
What can Hinder Communication? Not surprisingly, time constraints are cited as the greatest barrier by neurologists (47 percent) when it comes to patient communication. For patients, however, not wanting to be perceived as being “difficult” was cited as the barrier that most interfered with communication with their physicians (24 percent), followed by time constraints (21 percent). “The discomfort reported by both people living with MS and treating physicians suggests that important conversations about all of the symptoms associated with MS may not be happening,” said Maggie Alexander, chief executive, European Multiple Sclerosis Platform (EMSP). “People with MS and their physicians should be empowered and equipped to discuss all aspects of the disease. This open and honest dialogue is critical to achieving improved quality of life and better long-term outcomes.”
Information is Accessible, but More is Needed
While the survey shows communication gaps between patients and neurologists exist, findings also demonstrate respondents are seeking information about the disease:
Sixty-three percent of physicians recommend materials available at their office to their patients, while only 19 percent of patients cite these materials as most helpful;
Seventy-two percent of patients find online and social media resources most helpful for finding information about MS; these resources are also recommended by 73 percent of physicians to their patients;
Many neurologists indicate a desire for additional resources to provide to their MS patients, including information on maintaining cognitive function (49 percent), managing the emotional challenges of having MS (45 percent) and being sexually active (43 percent).
“At Biogen Idec, we believe that successful MS treatment extends beyond medication. Our goal with this survey was to better understand the needs of the patient and the physician, and through that understanding bring a new awareness to the importance of a comprehensive dialogue about MS,” said Gilmore O’Neill, vice president, Multiple Sclerosis Research and Development, Biogen Idec. “Our alliance with the State of MS Consortium will ultimately help us work with the MS community to address these issues and continue to improve care.”
In collaboration with the State of MS Consortium, an in-depth report of these findings and perspectives from the committee members is currently under development, and will be available to the MS community by the end of the year. As part of its ongoing commitment, Biogen Idec continues to evaluate the results of this survey and work with the community to identify new and innovative solutions to improve care for MS patients.
About the Survey
Harris Poll, on behalf of Biogen Idec, surveyed 982 adults diagnosed with multiple sclerosis (“MS patients”) and 900 neurologists who treat MS patients (“neurologists”) within Germany, Italy, Spain, the UK, and the U.S. between March 18 and April 25, 2014. Within the U.S., MS patient responses were weighted for gender, age, region, race/ethnicity, education and income where necessary to align with actual proportions in the U.S. MS patient population; U.S. neurologist results were weighted for gender, region, and years in practice where necessary to align with actual proportions in the U.S. neurologist population. A global post-weight analysis was applied to the total data in order to give each country equal weight.
About the State of MS Consortium
The survey was led by the State of MS Consortium, an international steering committee of treating neurologists and representatives from patient advocacy organizations across five countries: the U.S., UK, Spain, Germany and Italy. The steering committee members, who were involved in the development of the survey, include:
Maggie Alexander, chief executive, European Multiple Sclerosis Platform, representing 39 MS societies from 34 European countries
Martin Duddy, M.D., consultant neurologist, department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
David E. Jones, M.D., assistant professor, University of Virginia Health System, Charlottesville, VA, U.S.
Nancy Law, executive vice president, National Multiple Sclerosis Society, U.S.
Mar Tintore, M.D., Ph.D., senior consultant neurologist, Neurology-Neuroimmunology Department, MS Centre of Catalonia, Hospital Vall d’Hebron, Spain
Antonio Uccelli, M.D., associate professor of Neurology and head of MS Clinic and Neuroimmunology Unit, University of Genoa, Italy
Robert Weissert, M.D., Ph.D., senior physician and researcher, university professor of Clinical Neurobiology, University of Regensburg, Germany
Sibyl Wray, M.D., director, Hope Neurology MS Center, Knoxville, Tenn., U.S.
Source: Fort Mill Times © Fort Mill Times 2014 (10/09/14)
Evaluation of visual structural and functional factors that predict the development of multiple sclerosis in clinically isolated syndrome patients.
Perez-Rico C, Ayuso-Peralta L, Rubio-Pérez L, Roldán-Díaz I, Arévalo-Serrano J, Jiménez Jurado D, Blanco R.
PURPOSE. To evaluate visual pathway structure and function in patients with clinical isolated syndrome (CIS) using spectral domain optical coherence tomography (OCT) and multifocal visual evoked potentials (mfVEP), predicting CIS conversion to clinically definite multiple sclerosis (MS).
METHODS. This observational, longitudinal study assessed the eyes with no prior history of optic neuritis of twenty-nine consecutive patients with CIS according to the McDonald criteria. The relationships of the mfVEP results with the clinical findings, psychophysical (Humphrey perimetry) and structural (OCT) diagnostic test data were investigated.
RESULTS. The mfVEP amplitude responses (interocular and monocular probability analysis) showed abnormal cluster visual field defects in 48.3% of the CIS eyes, while mfVEP latency analysis showed significant delays in 20.7%. OCT average RNFLT (retinal nerve fiber layer thickness) was significantly reduced compared to the control group (P = 0.02). Significant differences between CIS eyes with abnormal and normal mfVEP latencies were found for the OCT RNFLT (P < 0.001) with a longer latency being linked to more severe axonal damage. Using multivariate logistic regression analysis, OCT average RNFLT was found to be independent predictor of clinically definitive MS diagnosis at twelve months.
CONCLUSIONS. The combined use of OCT and mfVEP is helpful to detect significant subclinical visual pathways abnormalities and axonal loss in CIS patients. Retinal axonal loss measured by OCT is an important prognosis factor of conversion to MS in patients with clinically isolated syndrome in absence of symptomatic optic neuritis.
Source: Invest Ophthalmol Vis Sci. 2014 Sep 4. pii: IOVS-14-14807. doi: 10.1167/iovs.14-14807 © 2014 by Association for Research in Vision and Ophthalmology & Pubmed PMID: 25190654 (10/09/14)
Kessler Foundation scientists have shown that working memory may be an underlying mechanism of cognitive reserve in multiple sclerosis (MS).
This finding informs the relationships between working memory, intellectual enrichment (the proxy measure for cognitive reserve) and long-term memory in this population.
"Working memory mediates the relationship between intellectual enrichment and long-term memory in multiple sclerosis: An exploratory analysis of cognitive reserve" (doi: 10.1017/S1355617714000630) was published online ahead of print by the Journal of the International Neuropsychological Society on July 14. The authors are Joshua Sandry, PhD, and research scientist James F. Sumowski, PhD, of Neuropsychological & Neuroscience Research at Kessler Foundation. Dr. Sandry is a postdoctoral fellow funded by a grant from the National MS Society.
Cognitive symptoms, including deficits in long-term memory, are known to affect approximately half of individuals with MS. This study was conducted in 70 patients with MS, who were evaluated for intellectual enrichment, verbal long-term memory, and working memory capacity.
"We found that working memory capacity explained the relationship between intellectual enrichment and long-term memory in this population," said Dr Sandry. "This suggests that interventions targeted at working memory in people with MS may help build cognitive reserve to protect against decline in long-term memory."
Source: Science Codex (10/09/14)
A multiple sclerosis patient has complained of a "postcode lottery" in the funding of a drug to help with his symptoms.
Sativex is not considered cost-effective and is not routinely funded by health bodies in England.
Philip Grace, 58, from Great Tey in Essex, has been paying privately to get the drug, which cannot be prescribed by his GP.
He was told it might be funded on the NHS if he lived elsewhere.
"My doctor used the term 'postcode lottery' to describe my situation. I know other people in Essex who take it under NHS prescription," he said.
Diagnosed with MS 13 years ago, Mr Grace said the condition has had a huge impact on his movement.
He said: "Before I started taking Sativex, walking felt like trying to walk through water. It was like my body was fighting itself.
"I would also have really bad spasms during the night, which would mean I couldn't sleep. Nowadays, I still don't have much control over my legs, but my strength is coming back.
Sativex helps with muscle spasms and is used by patients when other treatments are ineffective. It was the first cannabis-based medicine to be licensed in the UK.
In August, the NHS in Wales announced it would fund the medicine, following an appraisal by the All Wales Medicines Strategy Group.
But in draft guidance published by Nice (National Institute for Health and Care Excellence), the drug was not considered to "represent cost-effectiveness".
The Mid Essex Clinical Commissioning Group, which funds health services in Mr Grace's area, said it did not routinely fund Sativex, but patients could be referred for "exceptional funding" by their GPs.
Mr Grace said his referral was made in July, but he is yet to receive a reply.
Source: BBC News © British Broadcasting Corporation 2014 (09/09/14)
Dock3 protects myelin in the cuprizone model for demyelination.
Namekata K, Kimura A, Harada C, Yoshida H, Matsumoto Y, Harada T.
Dedicator of cytokinesis 3 (Dock3) belongs to an atypical family of the guanine nucleotide exchange factors. It is predominantly expressed in the neural tissues and causes cellular morphological changes by activating the small GTPase Rac1.
We previously reported that Dock3 overexpression protects retinal ganglion cells from excitotoxic cell death. Oligodendrocytes are the myelinating cells of axons in the central nervous system and these cells are damaged in demyelinating disorders including multiple sclerosis (MS) and optic neuritis.
In this study, we examined if Dock3 is expressed in oligodendrocytes and if increasing Dock3 signals can suppress demyelination in a cuprizone-induced demyelination model, an animal model of MS.
We demonstrate that Dock3 is expressed in oligodendrocytes and Dock3 overexpression protects myelin in the corpus callosum following cuprizone treatment. Furthermore, we show that cuprizone demyelinates optic nerves and the extent of demyelination is ameliorated in mice overexpressing Dock3.
Cuprizone treatment impairs visual function, which was demonstrated by multifocal electroretinograms, an established non-invasive method, and Dock3 overexpression prevented this effect.
In mice overexpressing Dock3, Erk activation is increased, suggesting this may at least partly explain the observed protective effects.
Our findings suggest that Dock3 may be a therapeutic target for demyelinating disorders including optic neuritis.
Source: Cell Death and Disease (2014) 5, e1395; doi:10.1038/cddis.2014.357 & Pubmed PMID: 25165881 (09/09/14)
While multiple sclerosis is most typically associated with progressively declining physical ability, multiple sclerosis patients are often times affected by a number of physical and mental health comorbidities in addition to their worsening physical ability. This observation was highlighted by a group of researchers in Scotland led by Drs. Robert J. Simpson and Stewart W. Mercer of the University of Glasgow.
To establish the finding that “Physical and Mental Health Comorbidity is Common in People with Multiple Sclerosis,” the team analyzed data supplied by a nationally representative Scottish Primary Care dataset from the Primary Care Clinical Informatics Unit. Over three thousand multiple sclerosis patients and over one million controls over the age of 25 were evaluated for 39 different comorbidities. Eight comorbidities were related to mental health, and 31 were related to physical health. Age, gender, and socioeconomic status were also analyzed. Findings were published in the journal BMC Neurology.
As is the case for multiple sclerosis patients living in countries such as the United States, Canada, and Taiwan, multiple sclerosis patients living in Scotland seem to have higher rates of comorbidities. The odds of having at least one comorbidity were more than two times as great for multiple sclerosis patients than for controls. The odds ratios for two, three, or four or more, while not as great, were also significant: 1.49, 1.86, and 1.61, respectively. Most commonly, patients were afflicted with neurological and gastrointestinal conditions.
In terms of purely mental health comorbidities such as anxiety and depression, multiple sclerosis patients were again more susceptible. The odds ratio was 2.94 and increased with an increasing number of physical comorbidities.
Interestingly, multiple sclerosis patients were significantly less affected by cardiovascular conditions such as atrial fibrillation, chronic kidney disease, heart failure, coronary heart disease, and hypertension. This finding contrasts the findings of some other research groups, and the team believes it requires further investigation.
This study is impactful because it reiterates the fact that multiple sclerosis patients often have a lower health related quality of life and require greater utilization of healthcare services. Not only is this troublesome for patients themselves, but also it is burdensome to caregivers and the healthcare system. Probing further into the reason for a higher rate of comorbidities could alleviate some of the troubles of multiple sclerosis patients. Some studies suggest yoga may improve quality of life for patients, and it is inevitable a number of other interventions can do the same.
Source: Multiple Sclerosis News Today © Copyright 2014 BioNews Services, LLC (08/09/14)
The clincial meaning of 'Walking Speed'(08/09/14)
The Clinical Meaning of Walking Speed as Measured by the Timed 25-Foot Walk in Patients With Multiple Sclerosis.
Cohen JA, Krishnan AV, Goodman AD, Potts J, Wang P, Havrdova E, Polman C, Rudick RA.
IMPORTANCE: Walking impairment, a common clinical manifestation of multiple sclerosis (MS), is often measured in clinical practice and clinical trials using the Timed 25-Foot Walk (T25-FW).
OBJECTIVE: To evaluate the relationship between walking speed measured by the T25-FW and the Physical Component Summary (PCS) score of the 36-Item Short Form Health Survey (SF-36) to better understand the clinical meaning of T25-FW walking speed in MS.
DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 3 clinical trials (Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis [AFFIRM], Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing-Remitting Multiple Sclerosis [SENTINEL], and International MS Secondary Progressive Avonex Controlled Trial [IMPACT]) that included T25-FW and SF-36 scores as outcomes in patients with MS. Patients had secondary-progressive MS and an Expanded Disability Status Scale score of 3.5 to 6.5 or relapsing-remitting MS and an Expanded Disability Status Scale score of 0 to 5.0.
MAIN OUTCOMES AND MEASURES: We used Spearman rank correlation and Pearson product moment correlation (r ) and descriptive statistics to evaluate retrospectively the relationship between the SF-36 PCS score and T25-FW walking speed at baseline and the 2-year changes from baseline.
RESULTS: Among all 2549 patients from the 3 trials, walking speed and SF-36 PCS score at baseline were significantly correlated (n = 2333; r = 0.48; P < .001). In placebo-treated patients at 2 years, the percentage of change from baseline in walking speed was significantly correlated with the change from baseline in SF-36 PCS score (r = 0.35; P < .001). Significant correlations between the change in SF-36 PCS scores and the percentage of change in walking speed at 2 years also were observed in groups receiving active treatment (r, 0.13-0.28; P ≤ .005). Among placebo-treated patients, 27.5% had a clinically meaningful worsening (≥5-point decrease) in SF-36 PCS scores during the 2 years. Walking speed declined by 21.8% in these patients after 2 years, but only by 5.4% in those without worsening of SF-36 PCS scores.
CONCLUSIONS AND RELEVANCE: In patients with MS, walking speed measured using the T25-FW correlated with SF-36 PCS scores such that a decline in walking speed of 20% to 25% corresponded to a clinically meaningful worsening of SF-36 PCS scores. A 20% to 25% decline in walking speed may be a clinically meaningful threshold for defining worsening using the T25-FW in MS clinical trials and for monitoring patients in clinical settings.
Sources: JAMA Neurol. 2014 Sep 1. doi: 10.1001/jamaneurol.2014.1895. [Epub ahead of print] & Pubmed PMID: 25178496 (08/09/14)
Is the intestinal barrier damaged in MS?(05/09/14)
Researchers at Lund University in Sweden have published new research findings on the role of the intestinal barrier in the autoimmune disease multiple sclerosis (MS).
Within medical science, it is not known for certain how MS develops or why the body’s immune system attacks cells in the central nervous system. Inflammation develops for an unknown reason, which hinders transport of neural impulses. This can produce various physical and mental symptoms, including a loss of sensation, motor difficulties, blurred vision, dizziness and tiredness.
The present study investigates whether the function of the intestines is also attacked in MS. The results, obtained from a disease model of MS in mice, shows inflammation and changes in the barrier function of the intestines early in the course of the disease. The study has been published in the scientific journal PLOS ONE.
“We know that the permeability of the intestines to harmful substances is raised in inflammatory bowel diseases such as Crohn’s disease and ulcerous colitis, as well as in some other autoimmune diseases such as type 1 diabetes. The condition is called ‘leaky gut syndrome’. Our studies indicate a leaky gut and increased inflammation in the intestinal mucous membrane and related lymphoid tissue before clinical symptoms of MS are discernible. It also appears that the inflammation increases as the disease develops”, said Shahram Lavasani, one of the authors of the study.
Dr Lavasani and his colleagues at Lund University have previously shown that probiotic bacteria could give a certain amount of protection against MS. They therefore wondered whether the intestinal barrier is affected and decided to investigate inflammatory cells and processes in the intestine. The hypothesis was tested in a research project in collaboration with Professor Björn Weström, doctoral student Mehrnaz Nouri and reader Anders Bredberg.
“To our surprise, we saw structural changes in the mucous membrane of the small intestine and an increase in inflammatory T-cells, known as Th1 and Th17. At the same time, we saw a reduction in immunosuppressive cells, known as regulatory T-cells. These changes are often linked to inflammatory bowel diseases, and biologically active molecules produced by Th1 and Th17 are believed to be behind this damage to the intestines.”
Neuroinflammatory processes in MS are believed to lead to damage and leakage in the blood-brain barrier that protects the central nervous system and regulates the transport of cells. The researchers have now observed similar damage in the intestinal barrier, especially to the ‘tight junctions’ that bind the cells together in the mucous membrane of the intestine, and have demonstrated that these are connected to disease-specific T-cells.
“In most cases, we don’t know what triggers autoimmune diseases, but we know that pathogenic cells frequent and disrupt the intestines. A leaky gut enables harmful bacteria and toxic substances in the body to enter the intestine, which creates even more inflammation. Our findings provide support for the idea that a damaged intestinal barrier can prevent the body ending an autoimmune reaction in the normal manner, leading to a chronic disease such as MS”, said Dr Lavasani.
Shahram Lavasani and his colleagues believe that future drugs to treat this type of disease should perhaps not only focus on the central nervous system, but also on the intestines by repairing and restoring the intestinal barrier.
“In the long run, we hope that our findings will lead to better understanding of what actually happens in the development of MS. Looking even further to the future, we hope for the development of a better treatment that aims at the intestinal barrier as a new therapeutic target.”
The research group is now studying other inflammatory parameters in the gut that could affect the development of MS. Their aim is to draw up treatment methods that can heal the mucous membrane in the intestine in the hope of preventing the development of the disease. Some of this work forms part of Mehrnaz Nouri’s thesis, which will be defended later in the year.
Full Article - ‘Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.’
Source: Lund University (05/09/14)
GeNeuro SA announced today positive results from a one-year, open-label extension of a Phase IIa study. GeNeuro tested its monoclonal antibody GNbAC1 in 10 multiple sclerosis (MS) patients, nine of which had primary or secondary progressive disease. GNbAC1 targets the MSRV-Env protein expressed by genes of endogenous retroviral origin, which GeNeuro believe plays a critical role in the pathogenesis of MS.
The long-term safety profile of GNbAC1 was confirmed, with excellent tolerability among patients following repeat administration, verifying results of the earlier Phase I study. With respect to clinical endpoints, the average Expanded Disability Status Score (EDSS), which measures disease progression, remained stable over one year. MRI analysis revealed that the brain images also remained stable and biomarkers associated with the target showed a consistent decline. These results confirm the safety and tolerability of GNbAC1 and support a positive pharmacodynamic response to the treatment. The positive results of this clinical study represent the successful first step in GeNeuro’s Phase II program. A proof-of-concept clinical study to test the efficacy of GNbAC1 in MS will follow in 2015.
Francois Curtin, CEO of GeNeuro stated: “We are very excited by the potential that GNbAC1 offers as a new avenue to treat MS patients. In addition to confirmation of long-term safety of the monoclonal antibody in patients, we have seen that the cohort of progressive MS patients was stable over one year from both clinical and MRI standpoints. Moreover, there is a clear decrease in the associated biomarkers supporting a positive pharmacodynamic response. This reinforces our conviction that GNbAC1 can completely transform the MS therapeutic landscape.” Curtin adds: “Preliminary results of this study presented at the American Academy of Neurology earlier this year generated a high level of enthusiasm among clinicians as they see that this treatment could bring new hope to patients as a safe therapy addressing a causal factor of the disease, breaking with the immunosuppressive logic of existing treatments.”
Source: PipelineReview.com © La Merie Publishing (04/09/14)
Researchers at Glasgow Caledonian University (GCU) are leading a three-year study to establish if abdominal massage is effective and cost-effective in reducing the symptoms of neurogenic bowel dysfunction, which affects over 60% of multiple sclerosis patients.
Multiple sclerosis (MS) is a common life-long neurological condition primarily affecting younger adults.
Loss of normal bowel function is caused by damage to the nerves resulting in constipation and faecal incontinence, which devastating consequences for a person socially and psychologically.
The £742,000 Abdominal Massage for Bowel Dysfunction Effectiveness Research (AMBER) project is funded by the National Institute for Health Research’s Health Technology Assessment programme and has partners including Buckinghamshire Healthcare NHS Trust, University of Dundee, University of Aberdeen and University of Stirling.
Researchers led by Dr Doreen McClurg will recruit 200 people with MS, of which half will receive abdominal massage, to see if it is more effective in reducing the symptoms.
They will also identify and investigate the adequacy of the abdominal massage training DVD and the adherence to undertaking the massage.
Over six weeks, home massage will be recommended as part of their usual bowel care programme, and weekly telephone calls will be made by the researcher to discuss the massage and bowel care.
Dr McClurg says: “Bladder and bowel problems in patients are often not addressed due to embarrassment of the patient and clinicians. This is an intervention which is simple and can be undertaken by the person themselves or a carer. The project will also raise the profile of such issues and help that is available.”
Dr McClurg is also contributing to a £1m medical trial which is testing the efficacy of a prophylactic daily antibiotic for urinary infections among patients with bladder muscle weakness or nerve disease and a HTA funded programme grant of £2m around the feasibility of using a mixed package of single and multi-use intermittent catheters.
Source: GCU Copyright © Glasgow Caledonian University 2014 (04/09/14)
Breakthrough hope for MS treatment(03/09/14)
Scientists say they have discovered how to "switch off" autoimmune diseases such as multiple sclerosis.
Researchers at the University of Bristol, who describe the work as an "important breakthrough", say it could improve the lives of millions around the world.
In their research, published today in Nature Communications, the team reveal how to stop cells from attacking healthy body tissue.
The team discovered how cells convert from being aggressive to protecting against disease, rather than the body's immune system destroying its own tissue by mistake.
It is hoped the insight will lead to the widespread use of antigen-specific immunotherapy as treatment for many autoimmune disorders.
Conditions which could be affected by the research include multiple sclerosis (MS), type 1 diabetes, Graves' disease and systemic lupus erythematosus.
MS alone affects around 100,000 people in the UK and 2.5 million people worldwide.
Professor David Wraith, of the university's School of Cellular and Molecular Medicine, led the "exciting" research - which was funded by the Wellcome Trust.
"Insight into the molecular basis of antigen-specific immunotherapy opens up exciting new opportunities to enhance the selectivity of the approach while providing valuable markers with which to measure effective treatment," Professor Wraith said.
"These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat."
In the study, scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body's own tissue, while converting them into cells capable of protecting against disease.
This type of conversion has previously been applied to allergies, in a treatment known as "allergic desensitisation", but its application to autoimmune disorders has only recently been appreciated.
The researchers have now revealed how the administration of fragments of the proteins that are normally the target for the attack leads to correction of the autoimmune response.
Their work also shows that effective treatment can be achieved by gradually increasing the dose of antigenic fragment injected.
In order to analyse how this type of immunotherapy works, the scientists looked inside the immune cells themselves to see which genes and proteins were turned off by the treatment.
They found changes in gene expression that help explain how effective treatment leads to conversion of aggressor into protector cells.
The outcome is to reinstate self-tolerance, where an individual's immune system ignores its own tissues while remaining fully armed to protect against infection.
Researchers say that by specifically targeting the cells at fault, the immunotherapeutic approach avoids the need for immune suppressive drugs.
These drugs are often associated with side effects such as infections, development of tumours and disruption of natural regulatory mechanisms.
The treatment approach is currently undergoing clinical development through biotechnology company Apitope, a spin-out from the University of Bristol.
"Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy" is published in Nature Communications today.
Source: The Courier.co.uk © 2014 DC Thomson & Co, Ltd. (03/09/14)
Genzyme's plans to grow its multiple sclerosis business in Europe continued with the launch of two new treatments in the Republic of Ireland.
The company, which serves as the biotech arm of French pharma firm Sanofi, today launched the injectable Lemtrada (alemtuzumab) in the country just weeks after oral multiple sclerosis (MS) treatment Aubagio (teriflunomide) hit the market.
Lemtrada will be made available to adults with active relapsing-remitting multiple sclerosis (RRMS), in accordance with its approval from the EC. It is to be given as an intravenous infusion in two annual treatment courses.
Aubagio is also available for adults with active RRMS, although it is one of several new MS treatments that come in an oral formulation, offering greater convenience to patients. It is to be taken once daily.
According to Genzyme, there are 8,000 people in Ireland with MS and around 85% will be affected by RRMS.
The launch of Lemtrada follows a recommendation in July this year from the National Centre for Pharmacoeconomics (NCPE), which provides guidance on what drugs should be reimbursed on Ireland's healthcare system to the Health Service Executive (HSE).
By contrast, Aubagio was turned down by the NCPE in June with after its assessment found that the drugs cost was not justified by its benefits.
However, in a conversation with PMLiVE, Henry Featherstone, director of public affairs at Genzyme UK & Ireland confirmed that Genzyme has since held discussions with the HSE and they have agreed that the drug can be reimbursed in Ireland.
As for where the drugs fit on the MS treatment pathway, Featherstone said that the broad indications for both products allowed doctors to discuss suitable options with patients. Further down the line, however, it's possible that Aubagio will be better suited as a first-line treatment for people with MS, while Lemtrada will be reserved for more aggressive forms of the disease.
"We hope to have these treatments available to as many people with MS as possible," Featherstone told PMLiVE. "We passionately believe in these products."
Backing Featherstone's belief, both drugs are making headway in western Europe where Lemtrada had revenues of €10m for the first six months of the year and Aubagio had revenues of €38m.
It's a different story for Lemtrada in the US, however, as the drug was turned down by the FDA at the start of 2014, much to the shock of Genzyme and Sanofi.
The decision, which was based on concerns over the drug's safety, drew criticism from the healthcare community and dozens of US doctors added their name to an open letter to the FDA to appeal the negative guidance.
Source: PMLive © PMGroup Worldwide Ltd 2014 (03/09/14)
Axonal degeneration in multiple sclerosis: can we predict and prevent permanent disability?
Lee J, Taghian K, Petratos S.
Axonal degeneration is a major determinant of permanent neurological impairment during multiple sclerosis (MS). Due to the variable course of clinical disease and the heterogeneity of MS lesions, the mechanisms governing axonal degeneration may differ between disease stages.
While the etiology of MS remains elusive, there now exist potential prognostic biomarkers that can predict the conversion to clinically definite MS.
Specialised imaging techniques identifying axonal injury and drop-out are becoming established in clinical practice as a predictive measure of MS progression, such as optical coherence tomography (OCT) or diffusion tensor imaging (DTI). However, these imaging techniques are still being debated as predictive biomarkers since controversy surrounds their lesion-specific association with expanded disability status scale (EDSS).
A more promising diagnostic measure of axonal degeneration has been argued for the detection of reduced N-acetyl aspartate (NAA) and Creatine ratios via magnetic resonance spectroscopic (MRS) imaging, but again fail with its specificity for predicting actual axonal degeneration. Greater accuracy of predictive biomarkers is therefore warranted and may include CSF neurofilament light chain (NF-L) and neurofilament heavy chain (NF-H) levels, for progressive MS. Furthermore, defining the molecular mechanisms that occur during the neurodegenerative changes in the various subgroups of MS may in fact prove vital for the future development of efficacious neuroprotective therapies.
The clinical translation of a combined Na+ and Ca2+ channel blocker may lead to the establishment of a bona fide neuroprotective agent for the treatment of progressive MS. However, more specific therapeutic targets to limit axonal damage in MS need investigation and may include such integral axonal proteins such as the collapsin response mediator protein-2 (CRMP-2), a molecule which upon post-translational modification may propagate axonal degeneration in MS.
In this review, we discuss the current clinical determinants of axonal damage in MS and consider the cellular and molecular mechanisms that may initiate these neurodegenerative changes. In particular we highlight the therapeutic candidates that may formulate novel therapeutic strategies to limit axonal degeneration and EDSS during progressive MS.
Source: Acta Neuropathol Commun. 2014 Aug 27;2(1):97. [Epub ahead of print] & Pubmed PMID: 25159125 (02/09/14)
Specialised programme improved quality of life, decreased pain and fatigue.
Paula Meltzer was only 38 when out of nowhere everything she looked at was blurry. For the single mother, who had a lucrative career as a gemologist and spent hours examining valuable pieces of jewelry, it seemed as if – in a split second – her life changed.
At first doctors thought Meltzer had a brain tumor. What they determined after further tests, however, was that she had multiple sclerosis, an autoimmune disease that affects the brain and central nervous system and was causing optic neuritis, an inflammation of the optic nerve that can cause a partial or complete loss of vision.
“I was living independently, doing my job, taking care of my child and then I had to look to my parents to take care of me,” Meltzer said.
Almost two decades later, Meltzer, out of a wheelchair and walking without a cane, was one of 14 women with moderate disability due to MS who participated in a pilot trial conducted by the Rutgers School of Health Related Professions. A specially-designed yoga program for these MS patients not only improved their physical and mental well-being but also enhanced their overall quality of life.
“I felt like I became steadier and stronger in my core,” Meltzer said. Prior to yoga, she described herself as a “wall walker,” someone who felt safer holding onto the wall in order to get around. “To be able to stand on one leg and feel balanced is amazing.”
Susan Gould Fogerite, director of research for the Institute for Complementary and Alternative Medicine in the School of Health Related Professions, said that although there is widespread evidence that yoga is being used as a form of exercise by those with MS, much of the feedback has been anecdotal and there isn’t much empirical data regarding its safety and efficacy.
This is why she and her colleagues, Evan Cohen and David Kietrys, physical therapists and associate professors in the School of Health Related Professions at Stratford, decided to undertake the small pilot study, believing that a specialized yoga program for MS patients – which incorporates mind, body and spirit – would be beneficial to everyday living.
What they discovered at the end of the eight-week trial was that those who participated were better able to walk for short distances and longer periods of time, had better balance while reaching backwards, fine motor coordination, and were better able to go from sitting to standing. Their quality of life also improved in perceived mental health, concentration, bladder control, walking, and vision, with a decrease in pain and fatigue.
“Yoga is not just exercise, it is a whole system of living,” said Fogerite, an associate professor, who, along with Kietrys, will present the results on September 26 at the Symposium on Yoga Research at the Kripalu Institute in Massachusetts. “The panel of experts who advised us on the trial wanted to make sure that we provided a fully integrated program that included philosophy, breathing practices, postures, relaxation and meditation.”
The yoga pilot trial was held at Still Point Yoga Center in Laurel Springs, a southern New Jersey town close to Philadelphia. Of the 72 individuals who were interested in participating, only 16 were eligible based on medical and other criteria and availability. Of those, 15 were enrolled and 14 completed the program after one person had to withdraw because of an unrelated health problem.
Meltzer and the other women who participated in the trial ranged in age from 34 to 64. Some had been diagnosed with MS within the last two years while others had been living with the illness for up to 26 years. For 90 minutes, twice a week for two months, they practiced techniques and exercises that would improve their posture, help to increase stamina, and teach them how to relax and focus.
“This study, I hope, is one of many that will give us the clinical information we need,” said Fogerite. “Yoga is not currently being widely prescribed for people with MS, although it might turn out to be a very helpful treatment.”
The yoga practices were done by the women in the study sitting, standing, or lying on yoga mats, and using metal folding chairs situated close to the wall to provide them with more support.
“What was so nice about this experience was that although everyone was at a different level of the disease, we felt like we were all together, so I think the comraderie helped,” said Meltzer. “And it wasn’t just about gaining more mobility and balance in our legs but our arms and necks felt stronger as well.”
Fogerite said a larger randomized controlled trial would be needed to determine whether yoga could be used as a prescribed treatment for individuals with moderate disability due to MS. More than 2.3 million people – two to three times more women than men – throughout the world are diagnosed with this disease which can cause poor coordination, loss of balance, slurred speech, tremors, numbness, extreme fatigue and problems with memory and concentration.
“When I was first diagnosed I no longer felt safe in my own body,” Meltzer said. "I didn’t trust my body at all. What the program did was really bring that trust back.”
Source: Rutgers Copyright 2014, Rutgers, The State University of New Jersey (02/09/14)
Teva’s Copaxone patent problems continue(01/09/14)
Teva Pharmaceuticals Industries Ltd is in trouble again for its multiple sclerosis (MS) injectable drug - Copaxone, as other drug manufacturers seek to launch their own generic versions of the drug. Teva has been fighting patent battles to ward off other pharmaceutical companies from making generic copies of Copaxone.
Copaxone makes up one-fifth of the company’s sales, but it is expected to lose 50% of its revenues by 2016, after its generic copies are launched. To deal with this impending threat, Teva introduced an improved version of the drug, with a higher dosage. But despite the introduction of the new Copaxone 40mg, troubles continue to pile up for the company.
Yesterday, Mylan Inc (MYL) and the duo of Novartis AG (ADR) (NVS)’s Sandoz unit and Momenta Pharmaceuticals, Inc (MNTA) announced that they have filed an Abbreviated New Drug Application (ANAD) for the Copaxone 40mg/mL with the US Food and Drug Administration (FDA). The ANAD, if approved, will allow the duo to manufacture and market a generic version of the drug, possibly at a low cost, which is a huge threat to the Israel-based company.
Copaxone – Teva’s Hero
Copaxone, launched in the US in 1997, is a drug for the treatment of relapsing multiple sclerosis (MS). The drug turned out to be a huge success for the company and generated $4.3 billion in sales last year, making 21% of the company’s sales. It also constitutes 42% of the company’s earnings.
However, the drug’s patent expired on May 24 this year. In order to deter launches of generic versions of the drug and to sustain its sales from Copaxone, Teva rolled out a new version of Copaxone in January - the new Copaxone is a 40 mg compared to the earlier 20 mg dose. The increased dose reduced the frequency of the drug administration significantly, from a daily dose to only three-times a week. The move worked for Teva, as in its last earnings announcement, CEO Erez Vigodman said that 51% patients had already converted to the new drug, and that the company is targeting a 65% conversion rate. The new version of the drug has patent protection until 2030.
Earlier Patent Battles
Teva, itself manufactures generic versions of many drugs, but it filed a patent infringement case against Sandoz in 2013, claiming that it was developing drugs similar to Copaxone, and violating Teva’s rights. The case was ruled against Teva, following which, Teva filed an appeal against the ruling.
Few months before Copaxone’s patent expiration, it filed a case in the US Supreme Court, seeking to delay the release of generic versions of the drug, until a ruling for the infringement case was given. Once again, the Supreme Court gave a decision against Teva’s expectations stating that any damages caused to Teva, will be recovered once the infringement case is finalised.
Teva still didn’t give up and filed a citizen petition with the FDA, asking the authority to order Mylan and Sandoz to conduct full-fledged clinical trials, which the FDA declined. In retaliation, Teva sued the FDA in Washington federal Court on May 9, claiming that the regulatory authority had wrongly rejected Teva’s appeal. Once again, Teva lost the case.
Teva’s efforts seem to have gone in vain, as yesterday Mylan and Sandoz both filed ANAD applications with the FDA for the development of generic versions of the new Copaxane 40mg, with a similar thrice a week regimen. Teva is expected to sue both companies for patent infringement, which will trigger a 30 month stay on the sale of any generic drug. But if Teva is unable to get a favorable decision before the end of the stay period, Mylan and Sandoz can launch their own biosimilar, as early as 2017.
This will be a big blow to the company, as Copaxone is a crucial part of its sales. The Copaxone 40mg has already earned $411.5 million in revenues since its launch, however cheaper versions of the drug will deeply reduce its sales. Copaxone 40mg is priced at $60,500 per year, only $1000 less than Copaxone 20mg. Any cheaper versions of the drug are expected to do well.
More importantly, Teva also faces competition from new MS oral drugs that have been launched recently. Biogen’s Tecfidera and Novartis’s Gilenya are both oral pills and can be administered more easily.
Going forward, it will be crucial for Teva to maintain sales from the MS segment, by developing new drugs for this disease. Currently, it has a MS drug called, Laquinimod, in its pipeline, which will be an oral treatment and is already in its phase 3 trials.
Teva’s stock has gained almost 30% year-to-date, as the company is trying hard to stop generic copies of its drugs from making it to the market.
Source: Bidness etc. © Bidness 2014 (01/09/14)