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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.


Estimating typical Multiple Sclerosis disability progression speed from clinical observations(20/10/14)

Murray G. Brown, Mark Asbridge, Vern Hicks, Sarah Kirby, Thomas J. Murray, Pantelis Andreou, Dong Lin

Abstract

Introduction

Multiple sclerosis (MS) is a chronic disease of the central nervous system. Estimates of MS natural history (NH) disability progression speed from clinical observations vary worldwide. This may reflect, in part, variance in censoring-bias) (missing observations) and assumptions about when irreversible disability progression events occurred. We test whether estimates of progression speed which assume midpoint survival time at irreversible disability endpoints are significantly faster than estimates which assume maximum survival time, and are more stable across study groups and time periods.

Methods

Our Nova Scotia NH study population includes 2,240 definite relapsing-onset multiple sclerosis (R-MS) natural history patients with 18,078 Expanded Disability Status Scale (EDSS) clinical observations in study period 1979–2010. Progression speed is measured by rate-of-change in range EDSS 0–6 and by survival time at irreversible endpoints EDSS 1–9. Midpoint censoring-bias-reduction methods are applied to clinical observations.

Findings

Typical EDSS increase per year in range EDSS 0–6, assuming midpoint survival time, is estimated to be 0.168 for all R-MS, 0.204 for eventually-DMD-treated patients and 0.155 for never-DMD-treated patients. Estimates assuming midpoint rather than maximum survival time are significantly faster: 16% faster for all R-MS natural history patients, 6% faster for eventually-DMD-treated patients, and 21% faster for never-DMD-treated patients. The variability of estimates across study groups and time periods decreased when midpoint survival time was assumed.

Conclusions

Estimates of typical disease progression speed from 1979–2010 Nova Scotia clinical observations are sensitive to censoring-bias and to analysts’ survival time assumptions. Censoring-bias-adjusted estimates of typical natural history disability progression speed in relapsing-onset multiple sclerosis patients are significantly faster, and less variable within and across study groups and time periods, than unadjusted estimates, and are, arguably, more relevant for various stakeholders. The application of censoring-bias-reduction methods to other multiple sclerosis clinical databases may reduce variability in estimates of disability progression speed worldwide.

Full Article

Source: PLOS © 2014 Brown et al (20/10/14)

Possible new target for Multiple Sclerosis treatment(15/10/14)

A study published in the October, 2014 issue of Nature Medicine points to a new target for the treatment of multiple sclerosis (M.S.). Inhibiting this target, in a mouse model of the disease, was shown to inhibit the disease in its most advanced stages.

The landmark paper, “B4GALT6 regulates astrocyte activation during CNS inflammation,” was authored by Lior Mayo, Francisco J. Quinta et al. at Harvard Medical School. Abdolmohamad Rostami, M.D. Ph.D., professor and chair of the department of neurology at Thomas Jefferson University, together with Assistant Professor of Neurology Bogoljub Ciric, Ph.D., authored a commentary article, “Astrocyte-derived lactosylceramide implicated in multiple sclerosis,” about the research for Nature Medicine.

“These findings provide a basis for targeting astrocytes, in particular LacCer signaling, as an alternative to most existing M.S. therapies, which modulate the immune system,” said Dr. Rostami. Patients and researchers have been frustrated by the limited effectiveness of available therapies for M.S., especially for “progressive” M.S., a devastating form of the disease that continues to progress with no interruption.

As Rostami and Ciric write in their commentary, the researchers started by investigating a puzzle in M.S. biology. M.S. is thought of as a disease in which the immune cells attack the neuron’s “insulating” tissue, myelin, which helps speed the signals passing from one cell to the next. A type of brain cell, called an astrocyte, appears to play two roles in the disease – protecting and re-myleninating cells early on, and then later, it appears to participate in the inflammatory reaction that fuels the disease.

Exploring this question, the researchers found that the gene B4GALT6 encodes an enzyme that makes LaCer (latosylceramide) — a lipid-signaling molecule. Increasing LaCer production worsens the disease, while inhibiting LaCer halts progression in a mouse model of late-stage disease, suggesting that this enzyme could be a potent target for developing a novel class of therapies against M.S.

Rostami and Ciric write that LaCer appears to contribute to disease progression by activating astrocytes, which in turn activate inflammatory signals that damage nerve cells; it also contributes to the repression of genes associated with remyelinization.

Drs. Rostami and Ciric were particularly impressed with the studies that bridged the finding to human disease. The Harvard team also showed that in samples taken from humans with M.S., B4GALT6 expression levels were increased, as were markers of astrocyte activation, suggesting that a similar pathway may be at play in humans.

Source: Thomas Jefferson University Copyright © 2014 Thomas Jefferson University (15/10/14)

New MS Research into cytokine regulation, neuroprotection, tolerance induction(15/10/14)

Evotec AG, a German company specializing in the provision of drug discovery resources to biotech companies and learning institutions, announced that is going to begin three new research projects for the treatment of multiple sclerosis (MS), which will be supported by funds from the German Federal Ministry of Education and Research.

The scientific approaches being used in the three novel research projects will focus on cytokine regulation, neuroprotection, and tolerance induction for further advancing efforts to develop therapies for multiple sclerosis. The work is based on research from the Deutsches Rheuma-Forschungszentrum, an institute of the Leibniz Association, which will feature the work of Prof. A. Hamann, as well as researchers from the University Medical Center Hamburg-Eppendorf, with the collaboration of Prof. M. Friese and Dr. J. Herkel.

The company intends to use their drug discovery platform, as well as their project management capabilities and market presence, to help identify and facilitate candidate drugs through novel therapeutic approaches that are able to effectively tackle MS. Evotec will later commercialize them, and expects to be able to create viable competitors for the current treatments, which are mostly based on disease-modifying approaches that are used in treating patients with the relapsing-remitting form of the disease. The projects are expected to run for one and a half and three years, and are funded by a budget of more than $6.3 million dollars.

“These novel approaches to fight MS, the disease with the highest socioeconomic impact worldwide, perfectly fit to our EVT Innovate strategy to approach disease-modifying innovation and to identify first-in-class molecules eagerly sought for by the biotech and pharmaceutical industry,” said the Chief Scientific Officer of Evotec, Cord Dohrmann. ”We are proud to partner with these leading German research institutions and groups to translate their exceptional disease know-how into drug candidates and furthermore into novel products.”

Evotec had recently announced it was launching a line-up groundbreaking studies focused on the disease that affects the protective covering of nerve cells, leading to disability and loss of quality of life. Some of the companies partners include Bayer, Boehringer Ingelheim, CHDI, Genentech, Janssen Pharmaceuticals, MedImmune/AstraZeneca, Roche and UCB.

Source: Multiple Sclerosis News Today © Copyright 2014 BioNews Services, LLC (15/10/14)

SMC first to introduce oral Gilenya® as a first line treatment option for people with a severe form of MS(14/10/14)

SMC first to introduce oral Gilenya® as a first line treatment option for people with a severe form of MS

• Scottish people with a severe form of relapsing remitting multiple sclerosis are first in UK to get access to once daily pill fingolimod as a first line treatment option1
• Once daily pill fingolimod reduces the risk of relapses by 67% compared to placebo2

Today, the Scottish Medicines Consortium (SMC) has accepted once daily pill fingolimod (Gilenya®) as a first line option for people with a severe form of relapsing remitting MS, which has been shown to reduce the risk of relapses by 67% compared to placebo.1,2 This is the first time that an oral treatment has been made available as a first line treatment option for people with this severe form of MS - known as rapidly evolving severe relapsing remitting MS (RES RRMS).1

The SMC heard from patient groups that MS is an incurable progressive disease with devastating effects on those with the condition and their families.1 Symptoms can include intense pain, mobility problems, severe depression, fatigue, incontinence and loss of vision.1 MS affects over 100,000 people in the UK, with rates highest in Scotland.3,4

85% of people with MS are diagnosed with the relapsing remitting form - when symptoms flare up aggressively - known as relapses.5 There are different types of RRMS, including highly active and RES RRMS.6 In September 2012, the SMC agreed to reimburse fingolimod for people with highly active RRMS who are failing on first line interferon injections.7 Today’s decision means that fingolimod is now also reimbursed for RES RRMS – when a person has two or more disabling relapses in one year with associated MRI changes.1 The SMC’s decision to broaden access to fingolimod means this is the first time that people with this more severe form of RRMS will have the choice of a once daily pill as a first line treatment option.1

Prior to today’s decision, only one SMC approved treatment was available for people with RES RRMS – a hospital-based infusion called natalizumab required every 28 days.1 Fingolimod is a once daily pill that can be taken at home after the first dose, avoiding the need to travel to hospital every month. It has been shown to reduce relapses by 67% compared to placebo in those with RES RRMS (ARR 0.24 for fingolimod and 0.74 for placebo).2 The analysis was conducted in a subgroup of patients from the original phase III FREEDOMS trial.

Scottish patients with RES RRMS will have access to once daily pill fingolimod as a first line treatment option before those in the rest of the country. This is because the SMC process allows manufacturers to submit new data at any time. NICE is set to review fingolimod alongside a range of other MS treatments in 2015. This means that people with this severe form of RRMS north of the border will have an increased choice of first line treatments before their southern counterparts.

Today’s announcement follows a series of recent decisions by the European Commission and NHS England to extend the use of fingolimod to a wider group of people, just three years after its original licence was granted in March 2011.

To date, more than 100,000 people worldwide have been treated with fingolimod in clinical trials and in the post-marketing setting.8 Fingolimod has been approved in 80 countries.8

References 1. SMC assessment of fingolimod (as hydrochloride), 0.5mg hard capsules (Gilenya®). October 2014
2. Devonshire V, Havrdová E, Radue EW et al. Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study. Lancet Neurol. 2012; 11:420-28
3. The Scottish Parliament. Briefing for the Public Petitions Committee. http://www.scottish.parliament.uk/ResearchBriefingsAndFactsheets/Petitions%20briefings%20S3/PB10-1353.pdf Last accessed 10 October 2014.
4. MS Society. What is MS? http://www.mssociety.org.uk/about_ms/what_is_ms/index.html Last accessed 10 Oct 2014
5. MS Society. http://www.mssociety.org.uk/what-is-ms/types-of-ms/relapsing-remitting-rrms Last accessed 10 October 2014
6. MS Trust. http://www.mstrust.org.uk/atoz/types.jsp Last accessed 10 October 2014
7. SMC assessment of fingolimod (as hydrochloride), 0.5mg hard capsules (Gilenya®). SMC No. (763/12). 12 March 2012
8. Gilenya World Watch. http://www.gilenya-world-watch.com/English.html Last accessed 10 October 2014
9. European Commission. Community register of medicinal products for human use. Gilenya. http://ec.europa.eu/health/documents/community-register/html/h677.html Last accessed 10 October 2014.
10. NHS England commissioning guideline for Gilenya. June 2014

Source: Novartis (14/10/14)

Positive data from multiple dose phase1 trial of CTP-354(14/10/14)

Concert Pharmaceuticals Inc. announced Phase 1 data of CTP-354, a novel, potentially first-in-class, non-sedating, once-daily oral treatment for spasticity. In this multiple ascending dose trial, no sedation or ataxia was observed with CTP-354 and the drug was generally well tolerated across all dose cohorts.

Concert expects to initiate a Phase 2 clinical trial evaluating CTP-354 in patients with spasticity associated with spinal cord injury by the end of 2014.

"We are very pleased to have completed our clinical evaluation of CTP-354 in this Phase 1 trial. We remain on track to advance the program into Phase 2 testing later this year, initially targeting spasticity in patients with spinal cord injury followed by the start of a Phase 2 trial in multiple sclerosis patients in early 2015," said Roger Tung, President and Chief Executive Officer.

The Phase 1 multiple ascending dose clinical trial was a randomized, double-blind, placebo-controlled study in 30 healthy volunteers. The primary objective of the trial was to evaluate the safety, tolerability and pharmacokinetics of 10-day repeat dosing of 2 mg, 6 mg and 12 mg of CTP-354.

Clinical highlights include: CTP-354 was generally well tolerated. There were no serious adverse events and no treatment discontinuations. The most common adverse events were dose-related mild and moderate dizziness and somnolence (drowsiness). No sedation or ataxia was observed at the doses evaluated. Across all doses, plasma half-life was approximately 20 hours at steady state. CTP-354 exposure was generally dose-proportional across daily doses ranging from 2 mg to 12 mg. Administration of CTP-354 under both fed and fasted conditions provided similar exposure, indicating that it can be dosed without regard to meals.

The company previously reported positive results from both a Phase 1 single ascending dose trial and a Phase 1 brain imaging trial as measured by positron emission tomography, or PET imaging. The long half-life and pharmacokinetic profile observed in the single ascending dose support once-daily dosing of CTP-354. In addition, CTP-354 provided high and sustained brain GABAA receptor occupancy levels in the brain imaging trial in both single and repeat doses.

Based on the results of the Phase 1 trials, Concert intends to advance CTP-354 into Phase 2 clinical evaluation later this year. The Phase 2 program is projected to include two trials: one evaluating spasticity associated with spinal cord injury and one evaluating spasticity associated with multiple sclerosis.

Source: NASDAQ © NASDAQ OMX Group, Inc (14/10/14)

MS drug Gilenya in new therapeutic indication: Added benefit not proven(13//10/14)

The immunosuppressive drug fingolimod (trade name: Gilenya) was approved for an expanded therapeutic indication in May 2014: It is now also available for adults with highly active relapsing remitting multiple sclerosis (RRMS) who had received other pretreatment than interferon beta (IFN-β). In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether the drug offers an added benefit over the appropriate comparator therapy in this patient group.

According to the findings, such an added benefit is not proven: For some of the patients, the drug manufacturer presented no data. For other patients, the available study data either showed no differences between the treatment groups, or the data were not evaluable.

G-BA specifies appropriate comparator therapy

The Federal Joint Committee (G-BA) distinguishes between two patient groups for the assessment: In patients with highly active RRMS despite full previous treatment (no interferon beta), fingolimod was to be compared with glatiramer acetate or interferon beta. In patients with incomplete previous treatment, the G-BA distinguishes between two cases for the appropriate comparator therapy: In patients who had received glatiramer acetate, this medication was to be optimized and continued. In patients who had received a different drug, treatment was to be changed to interferon beta or glatiramer acetate.

Only data of few study participants relevant for the assessment

One relevant study was available for the early benefit assessment, an approval study on fingolimod (TRANSFORMS), which compared treatment with fingolimod versus treatment with IFN-β1a in adults with RRMS. However, the disease was rated as "highly active" in only nearly half of the 866 participants. Only 263 of these 402 patients had received full previous treatment. Only 42 participants, i. e. a little less than five percent of the total study population, had not been treated with interferon beta (17 patients in the fingolimod arm, 25 in the interferon beta arm). However, only these patients correspond to the subpopulation relevant for this benefit assessment, because it is only this subpopulation that fingolimod had received expanded approval for. The informative value of the results was considerably limited because only data of few participants were evaluable.

Differences between treatment arms not statistically significant

No deaths occurred during the total study duration of 12 weeks. There were differences between the fingolimod and the interferon beta group with regard to relapses and disability progression, but these were not statistically significant.

No evaluable data were available for the patient group for which fingolimod was newly approved regarding other aspects of the outcome "morbidity", e.g. fatigue or activities of daily living, and for the outcome "health-related quality of life". One of the reasons for this is that different proportions of patients were not considered in the analysis.

There were group differences in side effects (serious adverse events and treatment discontinuation due to adverse events), which again were not statistically significant.

Dossier without relevant study on patients with incomplete treatment

In its dossier, the manufacturer presented no relevant study for patients who had not received full previous treatment.

In summary, an added benefit of fingolimod is therefore not proven for patients with highly active relapsing remitting multiple sclerosis (RRMS) who had received a different pretreatment than interferon beta.

Discrepancy between approval and study population

In 2011, fingolimod had been approved for two therapeutic indications: for rapidly progressive severe RRMS and for highly active RRMS that had been pretreated with interferon beta. For these two patient groups, IQWiG had published a dossier assessment according to AMNOG in January 2012.

In this first assessment the problem had already occurred that participants with different types of RRMS had been included in the relevant study, and that the authorities had then limited the approval to specific, relatively small patient groups. Since the first approval and assessment, the manufacturer apparently conducted no further studies for the expansion of approval.

G-BA decides on the extent of added benefit

The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer's dossier and IQWiG's assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.

Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (13//10/14)

Thousands of people possibly wrongly diagnosed with Multiple Sclerosis, experts warn(09/10/14)

The National Institute for Health and Care Excellence has changed guidelines for Multiple Sclerosis.

Thousands of people may be being wrongly diagnosed with Multiple Sclerosis or not diagnosed at all, health experts have warned as they changed guidelines to improve detection of the condition. The National Institute for Health and Care Excellence said that as many as one in 10 cases was misdiagnosed and called for more thorough scans and tests to be carried out.

Around 100,000 people are thought to have MS in Britain.

The updated guidance for the NHS said patients should have a comprehensive review of all aspects of their care at least once a year.

Other key recommendations for healthcare professionals to follow include referring people with suspected MS to a consultant neurologist and offering people with MS an appropriate single point of contact to speak about their care, concerns and different treatment options.

Nice also suggested multidisciplinary teams made up of experts including neurologists, MS nurses, GPs, psychologists, speech and language therapists, occupational therapists, and physiotherapists should oversee care.

People with MS should also be encouraged to exercise and be offered supervised exercise programmes for those who struggle with mobility and fatigue.

Currently, those with MS can be left for more than a year without having their condition and medication monitored but the updated Nice guidance aims to ensure that people with MS have their condition and treatments reviewed more regularly.

Dr Paul Cooper, consultant neurologist at the Greater Manchester Neuroscience Centre and chairman of the Guideline Development Group (GDG), said currently some people are receiving "excellent care and support" but others around the country are not.

"The care someone receives should not depend on where they live, we want to ensure that throughout the country people with this distressing and disabling disease have prompt access to specialists who understand their needs and can help improve their condition," he added.

The life-long condition of the central nervous system affects both the brain and spinal cord. Its causes are complex and not completely understood and there is currently no cure.

Typical early symptoms include, limb weakness, lack of coordination, loss of sight, and bladder and bowel problems, which usually develop in sufferers' twenties.

Rates of MS vary with latitude: It is more common in Europe than in the Tropics, and affects more northerners than southerners in the UK.

Professor Mark Baker, clinical practice director at Nice, said: "About 100,000 people in the UK have MS, with symptoms usually appearing in younger people. It can be a highly disabling condition that people live with for many years.

"MS can significantly affect a person's quality of life: they may have to give up work and may also struggle with their mobility. We know that people with MS tend to die earlier than others. This is why it is important to give people access to the best treatments and specialists who can help them live as normal and as long a life as possible."

The Nice guidance does not recommend taking fampridine or the cannabinoid drug Sativex, with the CDG advising that there are better treatments available already on the NHS.

Dr Cooper added: "The substantial cost of sativex and fampridine compared to the modest benefit does not justify their use; there are better ways to improve care for people with MS."

Source: Daily Telegraph © Copyright of Telegraph Media Group Limited 2014 (09/10/14)

Could Multiple Sclerosis begin in the gut?(08/10/04)

MS researchers are focusing on the content of the gut’s microbiome as a possible contributor to the body’s autoimmune attack on its nervous system.

Multiple sclerosis (MS) is an electrical disorder, or rather one of impaired myelin, a fatty, insulating substance that better allows electric current to bolt down our neurons and release the neurotransmitters that help run our bodies and brains. Researchers have speculated for some time that the myelin degradation seen in MS is due, at least in part, to autoimmune activity against the nervous system. Recent work presented at the MS Boston 2014 Meeting suggests that this aberrant immune response begins in the gut.

Eighty percent of the human immune system resides in the gastrointestinal tract. Alongside it are the trillions of symbiotic bacteria, fungi and other single-celled organisms that make up our guts’ microbiomes. Normally everyone wins: The microorganisms benefit from a home and a steady food supply; we enjoy the essential assistance they provide in various metabolic and digestive functions. Our microbiomes also help calibrate our immune systems, so our bodies recognize which co-inhabitants should be there and which should not. Yet mounting evidence suggests that when our resident biota are out of balance, they contribute to numerous diseases, including diabetes, rheumatoid arthritis, autism and, it appears, MS by inciting rogue immune activity that can spread throughout the body and brain.

One study presented at the conference, out of Brigham and Women’s Hospital (BWH), reported a single-celled organism called methanobrevibacteriaceae that activates the immune system is enriched in the gastrointestinal tracts of MS patients whereas bacteria that suppress immune activity are depleted. Other work, which resulted from a collaboration among 10 academic researcher centers across the U.S. and Canada, reported significantly altered gut flora in pediatric MS patients while a group of Japanese researchers found that yeast consumption reduced the chances of mice developing an MS-like disease by altering gut flora.

Sushrut Jangi, a staff physician at Beth Israel Deaconess Medical Center in Boston who co-authored the BWH study, thinks that regional dietary influences might even be at play. “The biomes of people living in different areas and who consume Western versus non-Western diets are demonstratively different,” he says. “People who emigrate from non-Western countries, including India, where MS rates are low, consequently develop a high risk of disease in the U.S. One idea to explain this is that the biome may shift from an Indian biome to an American biome,” although there is not yet data to support this theory.

The microbiome theory is gaining so much steam in academia that a coalition of four U.S. research centers called the MS Microbiome Consortium recently formed to investigate the role of gut microorganisms in the disease. The group presented data in Boston showing significantly different gastrointestinal bacterial populations in patients treated with the MS drug glatiramer acetate compared with untreated subjects. How exactly the drug suppresses MS activity is unknown but the findings suggest that perhaps it works in part by altering gut flora and, as a result, suppressing abnormal immune activity. “The gut is well-positioned for an important role in the development of autoimmune disease, including MS.,” says Ilana Katz Sand, an assistant professor of neurology at Mount Sinai Medical Center in New York City and member of the MS Microbiome Consortium. “But important questions remain, such as how MS medications affect the microbiome, how an individual’s microbiome may affect treatment responses, whether particular bacterial species are associated with more severe disease and ultimately whether we can manipulate the microbiome to benefit our patients.”

Katz Sand says that dietary and probiotic approaches to treating MS are worth pursuing, as is a less palatable approach: fecal transplantation. Yet answers in science and medicine are rarely simple, she added, pointing out that in all likelihood MS arises from a complicated confluence of genetic and environmental influences that might ultimately trigger autoimmune activity. Beyond just our gut flora well over 100 genetic variants—many related to immune function—are now known to contribute to the disease as are external factors including vitamin D deficiency (MS is more common at higher latitudes), smoking and increased salt intake.

Further confounding our ability to pinpoint root causes is that our genetic code influences how our bodies and brains respond to these external factors. It could be that both genes and environmental stimuli lead to pathologic microbiomes or that some unfortunate combination of these factors leads to a common autoimmunologic pathway that ravages myelin. “We know the microbiome shapes our immune system and that MS is an immune-mediated disease. We also know that genes influence our microbiomes and immune systems,” says David Hafler, professor of neurology and immunobiology at Yale University School of Medicine who was at the conference but not involved in the microbiome work presented. But there must be nongenetic factors contributing to the disease, too, given that the incidences of MS and other autoimmune disorders are increasing.

“Maybe it’s a lot of little factors like low vitamin D, increased body mass index and increased salt intake,” Hafler says, “but I wouldn’t be surprised if it was one big thing, much like how H. pylori was found to cause ulcers. No one’s identified a clear bug that’s driving MS but I think it’s important we keep looking.”

Source: Scientific American © 2014 Scientific American, a Division of Nature America, Inc (08/10/04)

MS Cannabis drug ‘too costly’ for England but not Wales(08/10/14)

A drug derived from cannabis, which many people with multiple sclerosis say helps ease their symptoms, has been ruled too expensive to be used by the NHS in England even though it is approved for Wales.

In new guidelines for the diagnosis and treatment of people with the disabling disease, the National Institute for Health and Care Excellence (Nice) says the price set by the manufacturer of Sativex (nabiximols) is too high for the benefit it gives patients. But the decision opens up the sort of “postcode lottery” that Nice was set up to end, with MS patients in Wales able to use the drug on the NHS while those in England either have to buy it themselves or go without. Some will use the illegal drug instead.

A second drug, Fampyra (fampridine), designed to improve people’s ability to walk, has been rejected by both England and Wales. Neither drug is routinely available in Scotland.

“The substantial cost of Sativex and fampridine compared to the modest benefit does not justify their use; there are better ways to improve care for people with MS,” said Dr Paul Cooper, a consultant neurologist who chaired the guideline development group.

In a Guardian podcast, he suggested Wales had been “a little naive” in their assessment of Sativex: “They have taken information from the drug company at face value without seeing the original data and they’ve used dosages and potential benefits that we would not agree with.”

But the MS Society’s chief executive, Michelle Mitchell, said the rejection of the two drugs by Nice was disappointing. “Surely we should be striving for the most innovative treatment and care to be made available to people with MS, not limiting options even further,” she said.

The charity published a survey of nearly 4,000 people with MS that found 82% of those taking Sativex considered it essential or a high priority. The main reasons people gave for not taking Sativex were that it was not available where they lived – prior to Nice’s decisions, the NHS makes local decisions about funding the drug – or that they would have to pay privately.

“I experience very painful spasms around my ribs, the MS hug, and tightness in my arms and legs. I’ve been told that Sativex could give me some relief but it seems so out of reach,” said Shona Garrett, 38, from Lowestoft, who was diagnosed two years ago and is on a waiting list for the drug in her area. “I also experience nerve pain like constant pins and needles in my feet, and I’ve heard Sativex could help with this too. No one has offered me any other options.”

She and her husband had discussed paying for the drug privately, but they had been told it would cost £500 a month, which is more than they can afford.

About 100,000 people in the UK have MS. It tends to hit younger people and can lead to serious long-term disability.

The guideline says people with suspected disease should be referred promptly to a consultant neurologist for diagnosis. Among other recommendations are that they should have a single expert to speak to about their care, concerns and treatment options so they are not shuttled about between different doctors and nurses. They should also be encouraged and helped to exercise.

The MS Trust said although it welcomed its publication, “regrettably, we believe that the guideline falls short. Though it contains a number of welcome recommendations, it also contains some significant gaps and omissions. Overall we believe it demonstrates a lack of ambition to provide what people with MS need, that is, a genuinely comprehensive description of best practice in MS care.”

Source: The Guardian © 2014 Guardian News and Media Limited (08/10/14)

Autoimmune disease progression appears to be reversed by naturally occurring molecule(08/10/14)

Type 1 diabetes, ulcerative colitis, and multiple sclerosis are among the more well-known autoimmune diseases. But according to the AARDA, there are more than 150 rare autoimmune diseases, which affect around 50 million Americans. Even with this large number, scientists are still in the dark regarding interventions that can help cure these diseases. But this might change with the discovery of a molecule called NAD+ that has the potential to reverse autoimmunity.

What is autoimmunity?
When an intruding pathogen, such as a virus or bacterium, enters our bodies, our innate immune system gets activated, immediately sending out its soldiers (antibodies and immune cells) to identify and eliminate the pathogen, thus protecting us. But sometimes something goes wrong with this innate immunity and it starts regarding the body’s own tissues as foreign and repeatedly sends out soldier cells to attack them.

Autoimmune diseases can affect any part of the body, including the heart, brain, nerves, muscles, joints, lungs, kidneys, etc. There is still no established cause for autoimmunity, but genetic factors are considered to play a major role.

This new research conducted by Brigham and Women's Hospital (BWH) has identified NAD+ (Nicotinamide adenine dinucleotide), a naturally occurring molecule in living cells, plants, and food that has the potential to turn “destructive” cells that attack healthy tissues into “protective” cells. The molecule has also been found to reverse disease progression by restoring tissue damaged by the autoimmunity process.

"Our study is the first to show that NAD+ can tune the immune response and restore tissue integrity by activating stem cells," said Abdallah ElKhal, senior author, in a statement. "These findings are very novel and may serve for the development of novel therapeutics." The study is published online Oct. 7, in Nature Communications.

NAD+ plays an essential role in several metabolic processes. To test the action of NAD+ in pre-clinical trials, the scientists used experimental autoimmune encephalomyelitis, a pre-clinical model for human multiple sclerosis. They found that NAD+ could regulate the differentiation of immune cells called CD4+ T cells that have an established role in many aspects of autoimmune inflammation. Mice having NAD+ were administered with CD4+ T cells. They showed a significant delayed onset of disease, as well as a less severe form, therefore demonstrating the molecule's protective properties.

"This is a universal molecule that can potentially treat not only autoimmune diseases, but other acute or chronic conditions such as allergy, chronic obstructive pulmonary disease, sepsis, and immunodeficiency," said coauthor Stefan G. Tullius.

The scientists also successfully demonstrated the tissue-restoring capability of NAD+. This, they say, can benefit patients with advanced tissue damage caused by autoimmune diseases. The scientists are now exploring the other medical benefits of NAD+.

"Since this is a natural molecule found in all living cells, including our body, we hope that it will be well-tolerated by patients," said ElKhal. "Thus, we hope that its potential as a powerful therapeutic agent for the treatment of autoimmune diseases will facilitate its use in future clinical trials."

Source: Medical Daily © 2014 IBT Media Inc (08/10/14)

Cognitive executive deficits in Multiple Sclerosis patients(07/10/14)

Research supports the slowed processing speed in the executive deficits found in individuals with multiple sclerosis (MS), according to a paper from the Kessler Foundation.

The investigators wanted to further explore cognitive deficits, since they affect nearly half the population of MS patients. These disabling symptoms can adversely affect patients' quality of life. Data was collected from 50 MS patients and 28 healthy controls and all patients were evaluated through executive functioning tasks both with and without a processing speed element. The tasks included the Trail Making and Wisconsin Card Sorting tests.

The researchers found the MS patients performed on tasks related to executive function compared to their healthy counterparts. While analyzing the data for speed control, the scientists discovered the differences between the healthy and MS group disappeared. The data also revealed no difference on executive tasks with non-processing speed demands.

Disease progression was also something the researchers investigated throughout this study in the MS group. For MS patients, higher atrophy was associated with greater deficits on speeded executive tasks. However, the relationship vanished when the researchers controlled for processing speed. The researchers noted there was no association between atrophy and performance when analyzing non-processing speed executive tasks.

“Our results point to slowed processing speed as the mechanism underlying deficits in executive function,” Nancy Chiaravalloti, PhD, said in a press release. “Understanding this association is an important step toward the development of effective cognitive rehabilitation strategies for individuals with MS. We should focus our efforts on 2 key domains - processing speed and memory.”

Executive deficits in MS may be explained by slow processing speed, the researchers concluded in their paper. Slowed processing speed may be a primary impairment which underlies other cognitive functions. They believe it is important to unwrap processing speed contributions to executive function, which would be an important step toward the development of appropriate treatment and rehabilitation techniques for MS patients.

"Additional neuropsychological measures should be included in future studies,” Chiaravalloti added. “We also need to focus on the contribution of specific brain pathology, such as frontal atrophy and lesion load, to executive deficits.”

Source: Rehabilitation Psychology & HCPLive Copyright HCPLive 2006-2014 (07/10/14)

Natalizumab neutralizing antibodies in MS appear inreased by smoking(06/10/14)

Smoking appears to increase the likelihood of developing neutralizing antibodies to natalizumab (Tysabri, Biogen Idec), which cause the drug to have little, if any, therapeutic effect in multiple sclerosis (MS), a new study suggests.

The study was presented by Tomas Olsson, MD, Karolinska Hospital, Stockholm, Sweden, at the recent MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting.

"The lung seems to be an important immunoreactive organ where irritation such as smoking may increase risk not only for inflammatory diseases, but also neutralizing antibodies to biologicals like interferon β and monoclonal antibodies such as natalizumab," he concluded.

"While smoking should not prohibit use of natalizumab, the percentage of patients developing antibodies, neutralizing the effect of the treatment, is not negligible," Dr Olsson commented to Medscape Medical News. "Therefore patients should be advised about our findings. This comes on top of an increased risk for MS with smoking, and probably a worse disease course."

In his presentation, Dr Olsson explained that smoking is thought to contribute to the induction of neutralizing antibodies to interferon β-1a, so he and his colleagues aimed to investigate the influence of smoking on the risk of developing antibodies to natalizumab, another biological drug in the treatment of MS.

The study was based on 1338 natalizumab-treated patients with MS included in either of two Swedish case-control studies in which information on smoking habits was collected. Treatment-related information was obtained from the Swedish national MS registry and antibody status from the Swedish Nab lab. Enzyme-linked immunosorbent assay was applied before therapy start and after 6, 12 and 24 months. Through use of logistic regression, patients with different smoking habits were compared regarding risk of developing anti-natalizumab antibodies.

Results showed that compared with nonsmokers, the odds ratio (OR) of developing anti-natalizumab antibodies was 2.4 (95% confidence interval [CI], 1.2 - 4.4) for patients who smoked at the time of screening, and a significant trend showed higher risk of developing antibodies with higher intensity of smoking.

The increased risk remained when smoking within 2 years prior to screening was considered (OR, 2.7; 95% CI, 1.5 - 5.1).

Still Try Natalizumab in Smokers

Commenting on the study for Medscape Medical News, Heinz Wiendl, MD, University of Münster, Germany, called this an "interesting observation," but he said the findings would not discourage him from using natalizumab in smokers.

"The prevalence of neutralizing antibodies to natalizumab is quite low — maybe affecting around 5% to 9% of patients. We can easily identify the patients who develop these antibodies because they don't respond to the drug."

He continued: "If a patient has neutralizing antibodies the drug effect will be zero. Natalizumab is a strong drug and there should be an obvious reduction of relapses and MRI lesions when a patient starts on it. If this does not happen, I think we can assume there are neutralizing antibodies present and then we would switch to a differemt treatment."

Dr Olsson has received nonrestricted MS research grants and/or compensations for lectures and advisory boards from Biogen Idec, Genzyme, Novartis, TEVA, and Merck. Dr Wiendl reports honoraria and consultation fees from Bayer HealthCare, Biogen Idec, Fresenius Medical Care, GlaxoSmithKline, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Genzyme BioVentures, and Teva Pharmaceutical Industries.

MS Boston 2014: 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS). Abstract PS5.4. Presented September 11, 2014.

Source: Medscape Multispeciality © 1994-2014 by WebMD LLC (06/10/14)

New gene variants may relate to MS susceptibility(03/10/14)

Approximately 110 multiple genetic variations were previously identified by genome-wide association studies (GWAS) to be associated with Multiple Sclerosis (MS). Now, that number has increased, with more than 159 genetic variants identified, thanks to new research presented by Philip De Jager, M.D., of Brigham and Women’s Hospital, Harvard Medical School and the International MS Genetics Consortium at the ACTRIMS-ECTRIMS conference in Boston.

The team led by Dr. De Jager performed the first comprehensive meta-analysis of existing MS-GWAS, spanning approximately 14,000 individuals with the disease. The researchers identified unknown genetic variants, and further studies involving 2,000 individuals led to confirmation of 48 new variants — for now.

With the confirmed identification of these new genetic variants, the team proposed to understand how the variants relate to MS susceptibility. Dr. De Jager noted, “the majority of the MS genes seemed to be related to immune function and expressed on immune cells.” The authors hypothesized the new variants could be related with alterations to brain function. To test their hypothesis, they examined the newly genetic variants in older, MS-free postmortem frontal lobes’ tissues. “[This is] exciting because there are at least some disease effects that may be related to alteration of gene expression inside the brain,” commented the author. Since the analysis was performed with the whole tissue, at the moment the authors can’t confirm the source cell type for these genes, as Dr De Jager noted, “Some of these changes may be driven by changes in the brain’s immune cells like changes in the microglia.”

Notably, Dr. De Jager highlighted how certain genome regions harbor multiple different variants that impact the risk for MS. Hence, to develop reliable predictive tests for MS, it is crucial to study each of these variants and fully understand their functional impact on MS.

The current study explains less than half of the heritability of MS, so Dr. De Jagers’ team and the International MS Genetics Consortium are committed to identify more genetic variants for MS susceptibility and to study it thoroughly.

Source: Multiple Sclerosis News Today © Copyright 2014 BioNews Services, LLC (03/10/14)

The effects of age on remyelination in MS are reversible(03/10/14)

Like conducting an errant orchestra to play together, researchers are guiding processes that go awry in multiple sclerosis to repair themselves.

The conductor walks to the stand and takes his place in front of the orchestra. He raises his baton and, with a dramatic flourish, one hundred individuals come to life. From nowhere, the stillness becomes a beautiful harmony as each member takes their part in a complex symphony.

Consider the workings and structure of the human brain – our most complicated organ – in terms of this orchestra. When it works, it is capable of something more remarkable than the greatest musical compositions in human history, but when it is affected by a condition such as multiple sclerosis (MS), "the brain's tightly orchestrated biological functions become discordant – the conductor begins to fail at their job and several instruments go out of tune," said Professor Robin Franklin, Head of Translational Science at the Wellcome Trust-Medical Research Council (MRC) Cambridge Stem Cell Institute and Director of the MS Society Cambridge Centre for Myelin Repair.

His research team and those led by other Stem Cell Institute researchers Drs Thóra Káradóttir, Mark Kotter and Stefano Pluchino are each looking at a different aspect of this errant orchestra. They hope that their collective knowledge will one day help 're-tune' the brains of MS patients to self-repair.

In its simplest terms, MS is a disease in which the immune system turns on itself, destroying the oligodendrocytes that make a protective sheath called myelin, which encases nerve fibres. This halts the transmission of neural messages, and eventually leads to nerve fibre damage, resulting in a progressive loss of movement, speech and vision for the 100,000 people in the UK who have MS. However, the complexities of treating the disease go beyond simply stopping the destruction of myelin, said Franklin: "The myelin damage causes a build-up of debris, which needs removing, and the environment surrounding the cells needs to be conducive to regenerating the sheath. When we think about repairing the damage, we need to be considering several different biological phenomena at the same time."

Although there are drugs available for modifying the early stages of MS – including alemtuzumab (Lemtrada), developed in Cambridge – there are no treatments that regenerate the damaged tissue. Moreover, although the disease evolves over decades, with periods of remission followed by relapses, there is no treatment once patients have reached the progressive stage (estimated to be about 50% of current patients).

Oligodendrocytes – the master manufacturers of myelin – are formed by a type of stem cell in the brain called oligodendrocyte progenitor cells (OPCs), and are responsible for re-wrapping, or remyelinating, the bare axons with myelin in response to injuries or diseases. But this regenerative ability decreases with age and MS. "As the disease progresses, the need for intervention that galvanises the natural healing process becomes ever more important," explained Franklin. "Working with colleagues at the Harvard Stem Cell Institute, we've shown that the effects of age on remyelination are reversible, which gives us some confidence that we can use the brain's own OPCs for myelin regeneration."

However, to understand how to stimulate the brain's own repair mechanisms first requires an understanding of how the brain detects injury and initiates repair.

Thóra Káradóttir believes that one way the brain 'senses' problems are afoot is through the drop in how fast neural messages are passed across the brain. "The difference in speed between an intact neuron and a damaged one can be like comparing the speed of a cheetah to a tortoise," she said. "I'm eavesdropping on the information superhighway by attaching electrodes to neurons and OPCs." Her findings show that damaged fibres release a molecule called glutamate. "It's their 'cry for help' to OPCs. If it doesn't happen, or if the OPCs don't 'hear', then repair is reduced." She is working with Numedicus, a company that specialises in developing secondary uses for existing drugs, to test drugs that she hopes will be able to amplify this signal and increase the repair process.

Meanwhile, Robin Franklin's team has shown that it's possible to kick-start OPCs, driving the formation of oligodendrocytes and sheath formation, using a drug that targets retinoid X receptor-gamma, a molecule found within OPCs. The results are positive and clinical trials will shortly commence in collaboration with Dr Alasdair Coles from the Department of Clinical Neurosciences and the MRC Centre for Regenerative Medicine at the University of Edinburgh.

What's interesting about the rejuvenation of remyelination is that the treatment primarily affected inflammation in demyelinating lesions, and specifically the recruitment of cells called macrophages. These are the body's 'big eaters' – their role is to search out and gobble up rubbish. "We have identified myelin debris as a potent inhibitor of stem cells. Learning how it is being sensed by stem cells enabled us to overcome this inhibition by using drugs such as ibudilast. A clinical trial to test these effects is currently undergoing preparation," explained Mark Kotter. Franklin and Kotter's work is representative of an interesting turn in MS research within the field. Increasingly, investigators are looking at how the environment around the damage can be improved to help natural remyelination. "It's a curious paradox," said Franklin. "MS is caused by the immune system but components of the immune system are also key to its recovery."

Stefano Pluchino's team, for instance, has shown that injecting brain stem cells into mice with MS works in a surprising way. Instead of making new oligodendrocytes (or other brain cells), the cells seem to work by re-setting the damaging immune response, creating better conditions for the brain's own stem cells to replace or restore what has been damaged. He is now developing more-efficient stem cells and new drugs, including nanomedicines, to foster the healing of the damaged brain.

Given the complex landscape of abnormal activities happening in the MS brain, will combination therapies be the way forward? "Certainly," said Franklin. "Over the next ten years we will see an increased understanding of the fundamental biology in MS, we will identify more targets which may yield effective drugs and we'll have more-refined strategies for running clinical trials. What makes Cambridge rare is the spectrum of skills here – from understanding the fundamental biology of myelin repair through to clinical trials."

Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (03/10/14)

Should health charities be more transparent about their funding?(03/10/14)

Patient groups often shout loudly for access to drugs but are quieter about their links to industry. Sophie Arie and Chris Mahony ask whether this is acceptable given increasing demands for transparency elsewhere in medicine,

The recent decision that the multiple sclerosis drug nabiximols should be available on the NHS in Wales was met by MS charities as a small triumph for patients. Access to the drug, a cannabinoid spray that eases spasticity, had previously been denied because of its cost.

“As a charity we have campaigned over a long period for Sativex [nabiximols] to be widely available because of the significant impact that MS spasticity can have on daily activities,” Amy Bowen, director of service development at the Multiple Sclerosis Trust, told the BBC.1

She expressed hope that the recommendation would lead to the drug being more easily accessible in the rest of the UK.

The MS Trust failed, however, to mention either in media interviews or in lobbying documents, that it receives funding from the German drug giant Bayer, which markets the drug in the UK. The company donated £5000 (€6400; $8200) to the MS Trust in 2013 and 2012.2 3

On its website, the charity provides information about its corporate funding only in its annual review, and even this is not prominently displayed. Corporate funding is listed as a lump sum of £54,121 towards the back of the annual review, without naming individual companies or specifying how the funds were used. There is one reference within further tables of figures to a restricted grant from Sanofi.4

The Association of the British Pharmaceutical Industry requires drug companies to disclose all the details of their relations with patient groups and charities systematically and prominently on their websites. These show that, in addition to the £5000 from Bayer, the MS Trust has received significant sums in recent years from several other producers of MS drugs, including £15 000 from Genzyme, a Sanofi company which makes teriflunomide and over £50,000 from Biogen Idec, which makes interferon beta 1a, fampridine, and dimethyl fumarate and has several more MS treatments in development.5

The MS Trust did not respond when asked whether greater transparency would be better, but it said in a statement that the charity’s independence and integrity was protected by its policy on working with the drug industry, which is on its website.6

“At the MS Trust we believe that if a drug has been assessed as safe and effective and given a licence, we should do our utmost to ensure it is accessible to all who might benefit. We do this for all licensed MS drugs, regardless of the manufacturer,” the statement said.

In June this year, the head of the MS Society, Michelle Mitchell, wrote a letter in the Daily Telegraph, co-signed by several MS experts,7 criticising the National Institute for Health and Care Excellence (NICE) for blocking access to the “life-changing” drugs nabiximols and fampridine even though “they are licensed and proven to be effective at helping people walk more easily and control painful muscle spasms.” Yet the letter did not mention that the MS Society had received money from the companies who make and market those drugs.

MS Society and drug company funding
The MS Society received over £21,000 from Biogen Idec, £46,000 from Genzyme, and £5000 from Bayer in 2013. The charity names its corporate donors on the “corporate supporters” page of its website,8 but to find the sums involved you have to look at the last element of the annual accounts on page 50 of its 54 page annual review.9

“We know this is a sensitive issue and that we have to draw the balance between receiving money that enables us to achieve our charitable aims and ensuring that we maintain our independence,” said Nick Rijke, executive director of policy and research at the MS Society. “We’re very careful and are confident we have the balance right. We keep the amounts low and we publish them precisely to ensure that there is no risk of being compromised.

The society’s policy on working with drug companies states that no more than 5% of its income in any one year can come from these sources and, the charity says, in 2013 0.6% of its income came from them.10

The case of the MS charities is only a recent example of what could be perceived as an almost universal conflict of interest for patient groups. Nearly all such groups receive funding from drug companies and most are, by definition, the greatest champions of the products those companies sell. But the amount of information, and the prominence it is given on charities’ websites, varies enormously. Some charities have clear and comprehensive information about funding on the primary pages of their websites. Many provide only partial information, often recorded in areas of their annual reports which may be hard to find.

So does it matter if charities fail to mention their corporate donors when campaigning in favour of the drugs they make?

Questions over independence
Drug companies are a key source of funding for many patient groups, and the companies say that their financial support for charities is a logical “partnership” between those with a common interest in improving treatment and care for patients. Most charities campaign for access to newly licensed drugs for their patients and would do so with or without corporate funding, on the basis that their patients deserve to benefit from all licensed drugs for their condition. Most consider the issue to be resolved by policies on working with industry that include a limit on the proportion of total income to be received from corporate donors and avoiding donations from only one company.

Yet, there is growing concern that charities, like any other sector, should be more transparent about their funding given that they are widely perceived by patients, the public, and policy makers to be independent.

“Any time any organisation takes money from anybody for any purpose there is potential for a conflict of interest,” says Jeremy Taylor, chief executive of National Voices, the national coalition of health and social care charities in England.

But when “a charity advocating for groups of patients takes money from a pharmaceutical company,” the case is even more compelling, he says. “There is the risk of allowing your charitable objectives to be distorted to serve the interests of commercial organisations or simply being seen as serving the commercial need of the other organisations.”

Patient groups have gained influence in recent years as the internet has allowed them to reach larger numbers of patients. Many are now run by professionals with qualifications and careers in the charity sector rather than patients and, as government has become more keen to work with stakeholders, their potential to influence policy has grown.

Little research has been done into how health charities are funded and how transparent they are about that funding.

“In recent years we have seen the rise of patient and public engagement,” says Angela Coulter, director of the Health Services Research Unit at the University of Oxford. “They [patient groups and health charities] are sitting round policy making tables in many countries, and if they are not open about the fact they receive money from drug companies then how can you evaluate the quality of their advice?”

Position of influence
In the case of a regulatory body such as NICE, the experts drawing up guidelines are aware of the financial ties of patient representatives to the companies whose drugs are being assessed. Patient experts giving advice to advisory committees declare any conflicts of interests at the committee meetings, but their input is considered to be unacceptable only if they have personally received a payment that relates to a drug or treatment under review. If they are an employee of a patient organisation that receives funds from a drug company, their advice may still be taken into account.

“Being aware of any financial relationship with the sponsor provides context for the advisory committee’s consideration of the information and views being put forward by the expert” NICE’s chief executive Andrew Dillon told The BMJ.

“Almost all patient groups have some sort of funding from the companies involved in that disease, so to refuse input to anyone taking this funding would preclude them all,” says Ken Paterson a former head of the Scottish Medicines Consortium, the Scottish equivalent of NICE. Ten charities (including the MS Society) advised the SMC to recommend drugs made by their donors for NHS use recently, according to a report by the Sunday Herald newspaper. The charities did not recognise any conflict of interest, but one accepted that it needed to reduce the proportion of its funding that came from corporate donors.11

“We at the SMC are very aware of their connections [to industry] and factor that in when listening to what they have to say,” Paterson explains. “But the wider public believe them to be totally independent,” he says. “Politicians and wider society need to be aware that they [patient groups] may not be entirely unbiased when they protest at decision over drug funding. There may be some levels of subliminal influence. This is why any money changing hands should be transparent.”

Support of patient groups is not the only way that drug companies have the potential to influence people. Companies often fund conferences for doctors and publications for patients produced by patient groups. Patient representatives are also often paid to deliver lectures at educational meetings or make presentations at conferences. And charities frequently use their large databases of patient members, to canvass opinion or gather data on patient experiences and wishes.

Overstepping
There have only been a few reported cases of charities’ activities being clearly compromised by their relations with a drug company and there is no reason to suspect that this is widespread. But the cases that have come to light have fuelled concern over a need for a culture of full disclosure throughout the sector, which could help patient groups avoid unintentionally giving credibility and sincerity to a drug company’s agenda.

“‘Marketing’ in research’s clothing can pass charities by without them realising,” says Paul Wicks, vice-president, innovation, at PatientsLikeMe a company set up in 2004 to help patients access and share data.

Sara Rigarre, a patient and campaigner for patient participation in healthcare in Sweden, thought this was the case when she noticed that a survey sent from the charity she belonged to, the Swedish Parkinson’s Disease Association, seemed to be worded to encourage patients to ask their doctor for Duodopa (carbidopa-levodopa), made by Australian drug company AbbVie.[12] The survey was funded by AbbVie but sent to members of the charity with no mention of a corporate sponsor. It was presented as research into the variations in care and needs around the country but omitted to ask respondents to state where they lived. The Swedish pharmaceutical industry trade body, LIF, has since referred the case to its information examiner (IGM), a qualified doctor who examines information and marketing practices in the industry, who concluded that the survey constituted “marketing of a prescription drug to the public” and fined the company Kr140 000 (£12 000; €15 000; $19 000) for breaching industry regulations.13

The charity, however, has not recognised the IGM’s finding and insists that the survey was intended to find out more about how patients are referred in different parts of the country. Its secretary general, Inger Lundgren, who sent out the survey from her personal email, told The BMJ she forgot to mention the sponsorship and accepts responsibility for that. The survey did not need to collect patients’ geographical locations, she explained, because the charity already has that information stored on its database of members. The charity has decided not to use the data from the survey. However, it continues to take funding from AbbVie, and other drug companies sponsor activities such as educational programmes for doctors and nurses and awareness campaigns for politicians and the general public, she said. She did not say whether this sponsorship is made clear to those targeted but did state that the charity follows the ethical guidelines and recommendations of the Swedish industry trade body LIF and publishes full details of donations it receives on the LIF website.

“There have been implications for the drug company but nothing has happened to the charity,” Rigarre told The BMJ.

Ensuring transparency
Opinions are divided among health charities between those who are adamant their donors wield no influence and those who believe that charities need to be more transparent about their relationships with industry to preserve their reputations. Some, such as the mental health charity MIND, go so far as refusing any support from industry.

MIND’s fundraising director, Cathleen Miles, says: “Only by remaining totally independent of pharmaceutical companies can we retain that voice of independence and provide objective information to anyone who comes to us for support in making decisions about what treatment is best for them.”

Others believe that clearer guidelines are needed for all health charities to adhere to. But getting such a broad group of charities, which work to different national regulations from country to country, to agree on common rules on transparency could be difficult. There is also concern that federations of patient groups—both national and international—receive funding from industry that is not clearly labelled in individual groups’ accounts because it is channelled through the umbrella group.

Under regulations established by the Charity Commission, charities in the UK are not legally required to name all their donors. A spokesperson for the Charity Commisssion explained that “the legal requirements set a standard that charities must follow but they can, and many do, go over and above the legal expectations. We encourage charities to be transparent. We expect that trustees are diligent in this duty to protect the independence and the reputation of their charity.”

Drug companies in the UK generally adhere to the ABPI’s code of practice,14 which is overseen by the Prescription Medicines Code of Practice Authority (PMCPA). When a company is found to be at fault, it might be required to issue a corrective statement or publish an advertisement. Obviously the authority cannot discipline a patient group.

Taylor says National Voices has recently begun working with the ABPI to produce a joint guide to explain the code and set down some principles for growing the relationship between that industry and partners. The guide could cover the importance of governance, protecting independence, transparency, income diversity, and what to think about when entering an arrangement with a drug company.

“We are hoping it can be an equivalent to the joint ABPI-Department of Health guidance on collaboration between pharma and NHS organisations ,” he says.15 “It is helpful for us to be crystal clear about how much money an organisation receives from whom to do what, but that is not enough. The process of governance and internal scrutiny and discussion are as important. The code itself seems to involve a lot of red tape for the company with various forms—none of which seem to get to the heart of ethics and governance of relationships.”

At an international level, the International Alliance of Patients’ Organisations (IAPO) acknowledges there is a problem.

“We aspire to be as transparent as possible. Different people have a different understanding of what that means,” Jo Groves, the organisation’s chief executive says. “The pharmaceutical industry have got there through a process and patient groups need to do that too.”

But IAPO can only advise its members on best practice; it cannot force them to comply or impose any sanctions if they don’t.

References
1↵ Wales NHS to offer MS cannabis drug Sativex. BBC News 2014 Aug 15. www.bbc.co.uk/news/uk-wales-28810407
2↵ Bayer. Patient group donations 2013. www.bayer.co.uk/scripts/pages/en/commitment_and_sustainability/our_projects/patient_group_donations/patient_group_donations_2013/index.php.
3↵ Bayer. Patient group donations 2012. www.bayer.co.uk/scripts/pages/en/commitment_and_sustainability/our_projects/patient_group_donations/patient_group_donations_2012/index.php.
4↵ MS Trust. Trustees’ report and financial statements for the year ended 31 July 2013. www.mstrust.org.uk/downloads/ms-trust-annual-review-13.pdf.
5↵ Biogen Idec. Patient organisation support. www.biogenidec.co.uk/patient_organisation_support.aspx?ID=12875.
6↵ MS Trust. Policy on working with pharmaceutical, biotech, medical equipment and research organisations. www.mstrust.org.uk/about/mission.jsp.
7↵ Mitchell M, Hobart J, Weller B, Notcutt W, Kapoor R, Craner M, et al. Nice and MS medicine. Telegraph 2014 Jun 9. www.telegraph.co.uk/comment/letters/10884997/D-Day-on-two-wheels.html.
8↵ MS Society. Our corporate supporters. www.mssociety.org.uk/get-involved/corporate-partnerships/our-corporate-supporters.
9↵ MS Society. Annual report and accounts 2013. www.mssociety.org.uk/sites/default/files/Documents/Governance%20docs/MSSociety-annual-report-and-accounts-2013_0.pdf.
10↵ MS Society. Vision and mission. www.mssociety.org.uk/about-us/about-the-ms-society/mission-and-values.
11↵ Patient groups taking cash from drug firms. Herald2014 Jun 15. www.heraldscotland.com/news/health/patient-groups-taking-cash-from-drug-firms.24489434.
12 ↵ Patients-included Pharma Disingenuous, and busted. http://e-patients.net/archives/2014/01/patients-included-pharma-disingenuous-and-busted.html.
13↵ Pharmaceutical Industry Information Examiner. Decisions on acceptance case No R11 /13, 19 December 2013. www.lif.se/default.aspx?id=98993&ptid=19178.
14↵ Association of the British Pharmaceutical Industry. Code of practice. 2014www.abpi.org.uk/our-work/library/guidelines/Pages/The-Code-of-Practice-for-the-Pharmaceutical-Industry-2014.aspx.
15↵ Department of Health, NHS Confederation. ABPI. Joint working: a quick start reference guide for NHS and pharmaceutical industry partners. 2012. www.abpi.org.uk/our-work/library/guidelines/Pages/joint-working-handbook.aspx.

Source: BMJ 2014;349:g5892 © The British Medical Journal 2014 (03/10/14)

Environmental exposures and the risk of multiple sclerosis(03/10/14)

Environmental exposures and the risk of multiple sclerosis Several environmental exposures, including infection with Epstein-Barr virus, low levels of vitamin D and smoking are established risk factors for multiple sclerosis (MS). Also, high hygienic standard and infection with parasites have been proposed to influence MS risk.

The aim of this study was to investigate the influence of various environmental exposures on MS risk in a Norwegian cohort, focusing on factors during childhood related to the hygiene hypothesis.

Methods: A questionnaire concerning environmental exposures, lifestyle, demographics and comorbidity was administrated to 756 Norwegian MS patients and 1090 healthy controls. Logistic regression was used to calculate odds ratio (OR) with 95% confidence interval (CI) for the risk of MS associated with the variables infectious mononucleosis, severe infection during childhood, vaccination and animals in the household during childhood.

Age, gender, HLA-DRB1*15:01, smoking and infectious mononucleosis were included as covariates. General environmental exposures, including tobacco use, were also evaluated.

Results: Infectious mononucleosis was confirmed to be significantly associated with increased MS risk, also after adjusting for the covariates (OR?=?1.79, 95% CI: 1.12-2.87, p?=?0.016).

The controls more often reported growing up with a cat and/or a dog in the household, and this was significant for ownership of cat also after adjusting for the covariates (OR?=?0.56, 95% CI: 0.40-0.78, p?=?0.001). More patients than controls reported smoking and fewer patients reported snuff use.

Conclusions: In this Norwegian MS case control study of environmental exposures, we replicate that infectious mononucleosis and smoking are associated with increased MS risk.

Our data also indicate a protective effect on MS of exposure to cats during childhood, in accordance with the hypothesis that risk of autoimmune diseases like MS may increase with high hygienic standard.

Author: Marte GustavsenChristian PageStine MoenAnja BjølgerudPål Berg-HansenGro NygaardLeiv SandvikBenedicte LieElisabeth CeliusHanne F Harbo

Credits/Source: BMC Neurology 2014, 14:196

Source: 7thSpace Interactive © 2014 7thSpace Interactive (03/10/14)

Cambridge scientist awarded £150k for ground-breaking MS trials(02/10/14)

Treatment for multiple sclerosis (MS) patients could be revolutionised in ground-breaking trials planned by a Cambridge scientist.

Dr Su Metcalfe, a University of Cambridge senior research associate based at Addenbrooke’s, has won a £150,000 award which will enable her team to proceed to pre-clinical trials in Nanotechnology.

The award is one of only five given out this year worldwide from major pharmaceutical company, Merck Serono, and the first to a UK scientist.

The technology developed for treatment of MS - an incurable autoimmune disease that attacks the central nervous system - by Dr Metcalfe uses tiny ‘smart’ nanoparticles that act as magic bullets to deliver powerful factors known to increase repair of damaged myelin. The key factor is “LIF”, a stem cell protein.

The money from the Merck-Serono’s “Grants for Multiple Sclerosis International” (GMSI) scheme will fund preclinical trials of Metcalfe’s nano-therapeutic device that taps into the body’s natural mechanisms for repair and avoids use of drugs.

“Nanotechnology is now recognised as a key platform for healthcare,” said Dr Metcalfe. “Our ‘smart’ technology allows us to target delivery of molecules able to repair myelin and also reduce inflammation.

“By using a nanoparticle platform where the safety in humans is already confirmed, a hugely important feature for rapid progress towards the clinic, we can now expect to move to clinical trials within three to five years.”

Multiple sclerosis commonly affects young adults and in the UK alone, more than 100,000 people have MS with 2,500 being diagnosed each year.

The disease causes damage to the nerve sheaths, or myelin, which normally insulate the electrical activity of nerve fibres in the brain and spinal cord.

Specific nerves become inflamed and lose function and this disrupts messages from the brain to parts of the body, resulting in early symptoms of MS, such as impaired vision.

The award will link a small team of experts including bioengineer Dr Tarek Fahmy of Yale University who prepares the smart nanoparticles, Professors David Baker and Gavin Giovannoni who lead preclinical and clinical trials in MS at Queen Mary’s University of London, and Dr Anna Williams who works on progressive MS at the University of Edinburgh.

This GMSI project exploits nanotechnology to harness the power of Leukaemia Inhibitory Factor (LIF), a potent stem cell cytokine able to both oppose inflammatory immunity and promote myelin repair - both highly relevant to treatment of MS.

Source: CambridgeNewsUK Copyright © 2014 Local World (02/10/14)

Prospective drug for Progressive MS, Glialogix receives extra funding(02/10/14)

San Francisco Bay Area-based Glialogix, Inc., a biopharmaceutical company that specializes in developing novel treatments for multiple sclerosis (MS), announced yesterday that they have closed a Sponsored Research Agreement with Fast Forward, a non-profit organization that aims to accelerate MS treatment development. Glialogix will receive funding for one of their pipeline products for neuroprotection, GLX1112, which has shown efficacy in slowing disability progression and potentially repairing neuronal damage — one of the main priorities of the National Multiple Sclerosis Society (NMSS).

Fast Forward, founded by the NMSS, will be supporting Glialogix through cutting-edge pharmacokinetic testing, preclinical models and mechanistic research on GLX1112. According to Thad Reeder, Ph.D., the company’s CSO and lead researcher for the drug, it has already shown promising results in progressive forms of MS.

Glialogix CEO, Mark Moore, Ph.D., explained that there is a great need for effective treatments for progressive MS, as this type tends to cause the most disability and does not respond to treatments indicated for relapsing MS. At present, while there are several drugs being tested for treating progressive forms of MS, most patients are treated with RRMS therapies, as these are the only drugs approved by the FDA for treating progressive MS in the United States. In other countries, progressive MS patients often have no access to therapies, and are forced to cope with symptoms and disabilities on their own.

Dr. Moore concluded by stating that he looks forward to collaborating with Fast Forward on the development of a viable progressive MS therapy, and is confident this new agreement is the boost GLX1112 is waiting for.

Source: Multiple Sclerosis News today © Copyright 2014 BioNews Services (02/10/14)

Study shows multiple sclerosis patients benefit from exercise(01/10/14)

A new study has found that people with multiple sclerosis may reduce perceived fatigue and increase mobility through a series of combined strength training and fitness exercises.

The research from the Miguel Hernández University of Elche, supervised by Professor Raúl Reina, aimed to analyze the effects of strength training on the fatigue that MS patients suffer. A total of 19 participants (5 men and 14 women) were split into two groups. Most took part in a 12-week training program, whilst others were included in a control group. The research was conducted in collaboration with the Neurology Department of Elche General Hospital.

A first phase of general fitness was followed by a personalized intervention program based on each patient’s maximum force. The scientists assessed the effects of training and found that the experiment group gained "a fair amount" of functionality while the control group remained stable.

One patient, who was diagnosed the illness in 2007, says she has noticed improvements in her daily routine: “I was used to a life with limitations and now I can pick up my son and go with him to the park on foot."

The training and data collection process took place on campus, both at the sports facilities and the university’s Sport Research Centre. Meanwhile, perceived fatigue was registered daily, weekly and monthly through specific questionnaires. Each patient’s muscle strength was assessed by isokinetic dynamometry and functional tests.

The study also includes an analysis of motivational aspects and an interview on the perception of the effects of sport. This part is especially interesting as it shows an improvement of the participants’ quality of life, although the University will continue working with the MS patients to see the long term effects.

Source: Science 2.0 © 2014 ION Publications LLC (01/10/14)