Clinical studies of cannabinoid capsules expected later this year (27/08/15)
Drug development company MMJ PhytoTech has said it plans to initiate clinical studies of new capsule formulations derived from cannabis for the treatment of MS later this year.
Their phase 1, safety-oriented clinical studies have been approved by various ethics committees and public health organisations in America. The company has been actively investigating a new capsule that reportedly offers advantages over smokeable cannabinoid formulations, as oral administration is much more controllable and user-friendly.
Furthermore, the company says it is confident that their capsules can withstand room temperature storage for extended periods of time. In this way, the need for refrigeration is eliminated resulting in lower shipping and storage costs.
The company believes these advantages will give rise to a low cost cannabinoid alternative with potentially high patient compliance. The safety of these Tetrahydrocannabinol and Cannabidiol capsules will be tested in a small group of volunteers to test for adverse effects. They are expected to have a low frequency of side effects and, if proven as such, the company plans to conduct Phase 2 clinical studies to investigate the efficacy and optimal dosing schedule for MS patients. After the studies are complete, the company will hope to develop Phase 3 clinical trials to assess efficacy, effectiveness and safety of the drug in around 1,000 MS patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (27/08/15)
Human trials for marijuana chewing gum (27/08/15)
Cannabis-focused biotech company AXIM Biotechnologies has launched clinical trials on humans for medical cannabis chewing gum as a treatment for multiple sclerosis.
The gum, MedChew RX, contains five milligrams of cannabidiol — a non-psychoactive component of cannabis — and five milligrams of THC — a psychoactive cannabinoid.
Medical marijuana chewing gum “should allow for predictable and controlled release of the active ingredients,” George Anastassov, chief executive of AXIM, said in a statement.
It should not be socially stigmatising, should have a pleasant taste and consistency and no undesirable side effects, he added. “Chewing gum meets all these criteria.”
AXIM already has a cannabinoid chewing gum product, known as CanChew, on the market, however it does not contain THC and does not offer any medical claims.
The psychoactive component of THC is an effective way to treat patients with degenerative conditions, in addition to the medicinal properties of cannabidiol, which can be used to treat neurological conditions such as epilepsy and multiple sclerosis.
Additionally, the act of chewing helps preserve cognition and memory, as well as promotes overall oral health, Anastassov told MarketWatch.com.
While the current trials of the gum are only for MS patients, Anastassov says Axim hopes to expand the range of conditions it can be prescribed for.
“For multiple sclerosis, the market for treatment is quite large,” Anastassov says. “Eventually, we will try to enlarge the conditions for this medication, such as pain.”
He says pain is one of the most predominant symptoms patients of a wide variety of conditions including MS live with from globally, and there have been few game-changing drugs in the pharmaceutical market to help treat it.
There is no cure for MS, but current treatments work to speed recovery from attacks, slow disease progression and manage symptoms, according to the Mayo Clinic. The most common treatments used to manage symptoms are physical therapy, muscle relaxants and medications to reduce fatigue, depression and pain.
The Phase 1 trial of the gum is slated to begin in the second quarter of 2016. Though medical marijuana is legal in 23 states and the District of Columbia, it is classified on the federal level as a schedule I drug, which gives it the same illegal status as heroin and LSD and is considered to have no accepted medical use.
While America’s Food and Drug Administration has yet to approve any product containing cannabis, it has approved Marinol — which contains dronabinol, a synthesized form of THC — for anorexia, chemotherapy and AIDS patients. The FDA’s website says it will continue to assess the effectiveness of marijuana for medical use, and will work with companies on medical cannabis research.
If the gum is approved by the FDA, it could be available in all 50 states, even if they have not legalized medical marijuana. “That’s why we’re going through the FDA,” Anastassov says. “There’s no ambiguity as to where it’s legal.”
Source: Market Watch Copyright ©2015 MarketWatch, Inc (27/08/15)
Grant funds audio magazines for people with MS (26/08/15)
The national Multiple Sclerosis charity (MS-UK) has received £5,000 to fund the audio versions of their bi-monthly magazine in Colchester.
The donation was provided by the Santander Foundation which offers grants to UK registered charities for projects that help disadvantaged people in local communities.
MS-UK provides information and support to anyone affected by Multiple Sclerosis. The grant will enable those who struggle with a printed magazine to continue to enjoy all the latest news, research and features focused on living life with MS.
Amy Woolf, Chief Executive at MS-UK said: “This funding will allow us to continue to make New Pathways available to as many people as possible. Many people living with Multiple Sclerosis can have visual problems, or even struggle to hold a magazine, so to be able to continue to provide New Pathways in a format that can be enjoyed by as many people as possible is fantastic. We are very grateful to the Santander Foundation.”
Judi Hambling, Branch Manager at Santander’s Colchester branch said: “The Santander Foundation makes hundreds of donations every year to good causes throughout the UK. Our branch is committed to playing a key part in the community and we are delighted to be supporting MS-UK, and hope the donation makes a real difference to local people.”
Source: Santander Foundation (26/08/15)
Study helps cook up ways to keep MS patients active (26/08/15)
A new study published in the American Journal of Occupational Therapy has found cooking can be used as a measure of activity limitation and cognitive function.
The study, Factors That Moderate Activity Limitation And Participation Restriction In People With Multiple Sclerosis, was conducted by researchers at the Kessler Foundation, a non-profit organisation focused on the field of disability and rehabilitation research.
In total, 72 MS patients were evaluated in terms of their cooking ability as a measure of their activity limitation, and employment status as a measure of their participation restriction.
All patients were assessed through neuropsychological testing of memory, visual perception, executive function and processing speed. In addition, participants completed questionnaires concerning affective symptoms, fatigue, activity and participation.
Researchers found that processing speed was the only factor significantly related to both activity and participation. When analysing specific isolated aspects, employment status was found to be significantly associated with processing speed, visual memory education level and fatigue, while cooking ability was linked to the processing speed, verbal memory and working memory.
The research team concluded that processing speed seems to be a primary cognitive factor in MS patients that can have an impact on the quality of both activity and participation in the patient’s everyday life.
“The only variable significantly related to activity and participation was processing speed,” concluded the study’s lead author Dr. Yael Goverover in a press release.
“For occupational therapists, this means that implementing strategies that improve processing speed may help people with MS maintain their daily activities and stay in the workplace. In light of the close association between cognitive factors and cooking, providers should be aware that decline in cooking skills may be sign of cognitive decline in MS.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (26/08/15)
Mental visual imaging training improves patients' well-being (26/08/15)
Patients with relapsing-remitting multiple sclerosis (RRMS) often have deficits in two neuropsychological functions, autobiographical memory (AM) and episodic future thinking (EFT), which impact quality of life.
In a new study published in Restorative Neurology and Neuroscience, researchers report that training RRMS patients in mental visual imagery (MVI) can improve AM/EFT functioning.
AM facilitates the ability to remember personal detailed events within a specific location and timeframe. EFT enables people to imagine future personal detailed events as they might happen. When AM or EFT is impaired, patients can have difficulty participating in daily life.
"Several functions have been attributed to AM, such as its role in the construction of sense of self temporally extended, the development of new social relationships and the nurturing of existing ones, and a directive function where the past serves as a basis to guide present and future behaviours," explained Liliann Manning, PhD, Cognitive Neuropsychology and Physiopathology of Schizophrenia (INSERM UMR 1114), University of Strasbourg (France). "Taken together, AM constitutes a central process in any individual's life." EFT contributes to coping skills, goal achievement, implementation of intentions, and to a sense of personal continuity over time.
The MVI program to improve patients' AM/EFT is based on the ability to mentally construct scenes and pay close attention to details in the mind's eye. Participating patients underwent six two-hour MVI sessions, once or twice per week (depending on the patient's availability). The program comprised four steps, with mental visualisation exercises of increasing difficulty, during which the attending neuropsychologist provided continuous guidance (as much as necessary) to the patient, probing to recall general aspects to more detailed ones, adopting a "funnel-approach," and learning to work in a sequential manner.
Fourty RRMS patients participated in this study, all of whom were receiving regular drug therapy and were being evaluated for disease progression through clinical examination. All participants were also evaluated for brain abnormalities using MRI to confirm that significant signs of atrophy were present.
After establishing a baseline for each patient, AM and EFT were assessed using an adapted version of the Autobiographical Interview. Patients were divided into three groups who received MVI (the experimental group), a sham verbal treatment (verbal control group), and no treatment (stability group). The use of the control and stability groups was intended to rule out nursing and test learning effects.
Patient commentaries about the MVI program collected during this investigation noted a more general feeling of self-confidence in life, with higher levels of control and vitality.
According to Dr. Manning, "In summary, the major finding of this study is that AM and EFT impairment could be efficiently improved by means of a facilitation program and that the use of an MVI strategy seemed easily integrated and resulted in significant benefits in their daily life functioning. More generally, we hope that this study and its positive outcomes could encourage future investigations in different clinical settings."
Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS)(26/08/15)
Lack of vitamin D may cause MS, study finds (26/08/15)
A lack of vitamin D may be a direct cause of multiple sclerosis (MS), a study has found. Researchers say the discovery may have important public health implications since so many people have insufficient levels of the essential vitamin.
The findings may help explain why rates of MS, a potentially disabling auto-immune disease that damages nerve fibres, are higher in high-latitude regions such as northern Europe, which have fewer sunny days. Sunshine triggering a chemical reaction in the skin is the primary source of vitamin D.
Previous studies have suggested an association between lower vitamin D levels and a higher risk of MS. But now scientists have demonstrated a genetic correlation that points strongly to a causal link.
Scientists who scoured the DNA of 33,996 participants identified four single-letter variants in the genetic code that were closely associated with a vitamin D blood marker.
A comparison between thousands of MS sufferers and healthy individuals found that people whose genetic makeup was associated with a lack of vitamin D – meaning they had fewer of the biomarker variants – were at least twice as likely to have MS.
Writing in the online journal Public Library of Science Medicine, the authors, led by Dr Brent Richards from McGill University in Canada, wrote: “The identification of vitamin D as a causal susceptibility factor for MS may have important public health implications, since vitamin D insufficiency is common, and vitamin D supplementation is both relatively safe and cost-effective.
“The importance of these findings may be magnified in high-latitude countries, which have disproportionately higher rates of MS and also higher rates of vitamin D insufficiency.”
The research showed that every standard deviation decrease in genetic variants linked to the vitamin D biomarker doubled the risk of MS. Standard deviation is a statistical measurement of variation from an average.
The finding provided “strong evidence in support of a causal role of vitamin D in MS susceptibility”, said the scientists.
They added: “Whether vitamin D sufficiency can delay or prevent multiple sclerosis onset merits further investigation in long-term randomised controlled trials.”
Vitamin D generated by sunlight is converted in the body into the blood marker 25-hydroxyvitamin D (25OHD). This is then further converted into the active form of the vitamin, calcitriol, which acts as a powerful hormone. 25OHD levels in the blood are considered the best indicator of a person’s clinical vitamin D status.
MS, which affects about 100,000 people in the UK, occurs when the immune system attacks the protective myelin sheath that surrounds nerve fibres and acts as an insulator. Nerve signals are disrupted, leading to symptoms that can range from mild tingling sensations to full-blown paralysis. In rare cases that progress rapidly, the disease can be fatal.
Dr Benjamin Jacobs, from the Royal National Orthopaedic hospital in London, said: “This study reveals important new evidence of a link between vitamin D deficiency and multiple sclerosis. The results show that if a baby is born with genes associated with vitamin D deficiency they are twice as likely as other babies to develop MS as an adult. This could be because vitamin D deficiency causes MS, or possibly because there are other complex genetic interactions.”
Prof Danny Altmann, an immunologist from Imperial College London, said: “Vitamin D is relatively cheap, safe and many of us would be all the healthier if we could achieve the serum levels that our ancient ancestors presumably acquired when roaming outdoors in temperate climates, unclothed and eating a diverse diet including oily fish.
“While it may be too much to expect therapeutic vitamin D to treat or reverse ongoing MS, this paper will add to the weight of argument for routine vitamin D supplementation of foodstuffs as a broad preventative public health measure.”
Dr Susan Kohlhaas, the head of biomedical research at the MS Society, said: “More than 100,000 people are affected by multiple sclerosis in the UK, so the potential link between vitamin D and the risk of developing MS is an incredibly crucial area of research.
“There are many unanswered questions around what causes MS so this large-scale study is an exciting step towards understanding more about the complex nature of the genetic and environmental factors that contribute to it.
“There are government guidelines around how much vitamin D people should take, and taking too much can lead to side-effects, so we’d encourage people to talk to their health professional if they’re thinking of doing this. We’d also welcome more research into this area, as we know it’s really important to people living with MS.”
Source: The Guardian © 2015 Guardian News and Media Limited (26/08/15)
Nano sensor detects early stages of MS (25/08/15)
A nanometric sensor may be able to identify biomarkers of conditions such as multiple sclerosis (MS), neuromyelitis optica, and certain types of cancer, according to research published in Sensors Journal.
Researchers in Brazil developed a nano biosensor originally for detecting herbicides, heavy metals, and other pollutants. However, the transition into neurological and demyelinating diseases was prompted by a partnership with colleagues. The importance of this device is to be able to detect and diagnose these chronic illnesses before they advance beyond the beginning stages. These devices should also reduce the chance for false diagnoses, the researchers believe. However, MRI scans would still be necessary to confirm diagnoses because of the multifaceted criteria for these diseases.
“It’s a highly sensitive device, which we developed in collaboration with Alberto Luís Dario Moreau, a professor at the Sao Paulo Federal Institute of Education, Science, and Technology,” physicist Fábio de Lima Leite, a professor at the Federal University of Sao Carlos, Sorocaba, and the coordinator of the research group, said in a news release. “We were able to increase sensitivity dramatically by going down to the nanometric scale.”
By placing a drop of a patient’s cerebrospinal fluid on a glass slide and using the nano biosensor, the researchers can measure the interaction.
“If the interaction is low, we’ll be able to rule out MS with great confidence,” Leite explained. “High interaction will indicate that the person is very likely to have the condition. Different nervous system diseases have highly similar symptoms. MS and neuromyelitis optica are just two examples. Even specialists experience difficulties or take a long time to diagnose them. Our technique would provide a differential diagnostic tool.”
In the future, the investigators want to examine biomarkers for these conditions that have yet to be mapped, such as antibodies and antigens, and others. Testing for the detection of head and neck cancer has also begun.
Source: MD All Specialities Copyright MD Magazine 2006-2015 Intellisphere, LLC (25/08/15)
Many pediatric autoimmune disorders share altered genetic origins, study finds (25/08/15)
Many pediatric autoimmune disorders have genetic alterations at shared sites, according to a meta-analysis performed by researchers from the Children's Hospital of Philadelphia and elsewhere.
The researchers conducted a meta-analysis of 10 childhood-onset autoimmune diseases — such as inflammatory bowel disease, type 1 diabetes, and juvenile idiopathic arthritis — to uncover 22 gene locations that were shared among multiple pediatric autoimmune diseases, they reported in Nature Medicine. The researchers traced these signals to genes involved in immune-related pathways like cell activation, cell proliferation, and signalling.
"Our approach did more than [find] genetic associations among a group of diseases," senior author Hakon Hakonarson, the director of the Center for Applied Genomics at CHOP, said in a statement.
"We identified genes with a biological relevance to these diseases, acting along gene networks and pathways that may offer very useful targets for therapy."
Hakonarson and his colleagues performed whole-genome imputation on a combined cohort of 6,035 pediatric cases, representing 10 distinct autoimmune diseases, and 10,718 population-based controls with no history of immune disorders. From this, they found more than 7.3 million variants.
Using case samples from each of the 10 conditions and shared controls, they performed whole-genome case-control association testing, and then to find shared gene locations among the pediatric-onset autoimmune diseases they performed an inverse χ2 meta-analysis, which they said took into consideration both variations in sample sizes and their use of a shared cohort.
From this analysis, they identified 27 linkage disequilibrium-independent loci with genome-wide significance among the conditions, including five novel gene locations.
Twenty-two of these gene locations, the researchers reported, were shared among multiple pediatric autoimmune diseases. For instance, a locus mapping to an intronic SNP in IL21 was shared by eight conditions, while a novel loci in TENM3 was shared by six conditions.
The SNPs Hakonarson and his colleagues uncovered fell into four broad categories: functional, regulatory, conserved, and SNPs with prior literature support connecting them to an autoimmune disorder.
The vast majority of the SNPs, they said, don't appear to directly have functional consequences — they noted the SNPs were enriched for CpG islands, transcription factor binding sites, and more — suggesting that they either tag the causal variants or influence disease risk through regulatory or epigenetic mechanisms.
Using gene-based association testing, the researchers found 182 pediatric autoimmune disease-related genes. By examining a human gene expression microarray dataset of 12,000 genes and 126 tissue or cell types, the researchers observed that these genes were more highly expressed in immune cells than non-immune cells. They further discovered that these pediatric autoimmune disease-related genes were differentially expressed across immune cell types.
Based on their expression profiles, the researchers clustered the genes into related sets.
Cluster one, for instance, included ICAM1, CD40, JAK2, TYK2, and IL12B, which have roles in immune effector cell activation and proliferation. These genes were also associated with both primary sclerosing cholangitis and ulcerative colitis. The expression of these genes was higher in a subset of CD11b+ dendritic cells. This, Hakonarson and his colleagues said, is consistent with the clinical picture, as some 80 percent of primary sclerosing cholangitis patients have also been diagnosed with ulcerative colitis.
Similarly, cluster two genes were related to cytokines and were highly expressed across mature natural killer cells. The cluster was enriched for associations with multiple sclerosis and celiac disease, the researchers added.
Hakonarson and his colleagues developed a method to examine genome-wide pairwise-association signal sharing — dubbed a GPS test — across the various pediatric autoimmune conditions. The test, they reported, found evidence of sharing among type 1 diabetes and celiac disease; type 1 diabetes and autoimmune thyroiditis; ulcerative colitis and Crohn's disease; and ankylosing spondylitis and psoriasis, associations they said had been reported previously. They also uncovered evidence of sharing among juvenile idiopathic arthritis and common variable immunodeficiency.
Using ImmunoBase, they also found evidence of sharing between ulcerative colitis and Crohn's disease as well as between juvenile idiopathic arthritis and common variable immunodeficiency.
"Collectively, these results support genetic sharing between the various autoimmune diseases," the researchers said in their paper.
Hakonarson and his colleagues added that knowing that certain diseases have a shared genetic etiology could point to common mechanisms that could be targeted by a therapeutic. Further, they noted that a number of the genes they identified are already being explored clinically.
This study "offers opportunities for researchers to better target gene networks and pathways in specific autoimmune diseases, and perhaps to fine tune and expedite drug development by repurposing existing drugs, based on our findings," Hakonarson added.
Source: genomeweb Copyright © 2015 Genomeweb LLC (25/08/15)
Novartis acquires remaining rights to Ofatumumab (24/08/15)
Novartis has signed an agreement to acquire all of the remaining rights to Ofatumumab from GlaxoSmithKline. The fully human monoclonal antibody, which targets the CD20 molecule, is being developed for relapsing remitting multiple sclerosis (RRMS) and other autoimmune indications. Novartis previously acquired the rights to Ofatumumab for oncology indications and it is marketed under the brand name Arzerra®.
RRMS is thought to be associated with activation of B cells. Ofatumumab works by binding to CD20 on the surface of B cells and depleting them in lymphatic tissues. Positive Phase IIa results for subcutaneous Ofatumumab demonstrated significant reduction of up to 90 per cent in the cumulative number of new brain lesions in patients with MS between weeks 4-12 in the study, according to officials at Novartis. No unexpected safety findings were reported in the study. Since this was a dose finding trial, Ofatumumab is ready to begin Phase III pivotal studies.
Novartis will be responsible for the worldwide development, regulatory, and commercialisation activities for Ofatumumab. The company will make an initial upfront payment of $300m to GSK for the acquisition of the compound and a further payment of $200m payable following the start of a Phase III study in MS by Novartis. Upon completion of pre-determined milestones, contingent payments of up to $534m may be made. Novartis will also pay royalties of up to 12 per cent to GSK on any future net sales of Ofatumumab in auto-immune conditions.
Source: GEN © 2015 Genetic Engineering & Biotechnology News (24/08/15)
NICE Technology appraisals: Lay member recruitment (21/08/15)
NICE are recruiting for a lay member for NICE’s Technology Appraisal Committee. The Technology Appraisal Committee considers and interprets evidence of both clinical and cost effectiveness to produce guidance for the NHS on the use of new and established health technologies. These health technologies are usually medicines but the Committee also makes recommendation about medical devices and other therapies.
We are looking for someone who has:
• an understanding of the issues important to patients, service users, carers or communities gained, for example:
o through personal experience you have of treatment and care provided by the NHS
o as a relative or carer of someone who has used relevant health services
o as a volunteer or employee of a relevant patient, service user, carer, community or voluntary organisation, or support group
• knowledge of the experiences and needs of a wide range of people which gives you the ability to champion patient, service user and carer perspectives on this committee
• the ability to use word processing and the internet, and a willingness to communicate by email
• time to commit to the work of the committee by attending meetings, reading papers including summaries of research evidence, and commenting on draft documents
• Good communication and team-working skills.
For further details and information on how to apply please see: http://www.nice.org.uk/get-involved/join-a-committee/lay-member-technolo...
The closing date for applications is 5pm on Friday 16 September. If you’d like to discuss the role or have any questions please contact Laura Norburn – email@example.com, 0161 870 3023 up to 4th September and Chloe Kastoryano - firstname.lastname@example.org, 020 7045 2188 thereafter.
Poor sleep linked to MS-related fatigue (20/08/15)
A new study published in the journal Frontiers in Neurology has found sleep disturbances may play a major role in secondary fatigue in multiple sclerosis (MS).
An MS researcher at the Kessler Foundation, Lauren Strober, PhD, conducted a study in 107 patients aged 20–64. All participants were employed with a definite MS diagnosis. They all completed an online survey that measured disease variables, psychological functioning, well-being, health behaviours, adjustment and coping to MS, and overall quality of life. Sixty-one percent of patients were classified as "poor sleepers," and 25 per cent of those MS individuals were experiencing secondary fatigue due to sleep disturbances and another seven per cent were affected by depression.
Dr. Strober noted MS-related fatigue was a common and disabling symptom for patients with MS, and finding out what contributes to this fatigue can improve quality of life and keep people engaged in activities.
She said: “Routine screening for sleep problems and treatment of sleep disturbances may reduce fatigue and its debilitating effects.”
Further research is now needed to obtain objective measurement of sleep and fatigue rather than reliance on self-report measures.
Source: MPR Copyright © 2015 Haymarket Media, Inc (20/08/15)
Third case of PML reported to Novartis (19/08/15)
Novartis has been notified of a third case of progressive multifocal leukoencephalopathy (PML) in a patient with relapsing multiple sclerosis (MS) treated with Gilenya.
According to a notice on the company's Gilenya Information Center web page, the diagnosis of PML was based on suggestive clinical symptoms, magnetic resonance imaging findings, and tests for JC virus. The patient did not have prior exposure to Tysabri, treatment, which is already associated with increased PML risk.
The patient reportedly has a history of colorectal cancer treated with chemotherapy and radiation treatment, as well as Crohn's disease.
Novartis says it is currently in "active discussions with external advisors to review details of this case and the role of various risk factors contributing to the development of PML."
Earlier this month, the US Food and Drug Administration (FDA) warned that a case of definite PML and a case of probable PML have been seen in patients taking Gilenya for relapsing MS, as reported by Medscape Medical News. Neither of these patients had previously received Tysabri treatment.
"Patient safety is of paramount importance for Novartis and we recently updated the Gilenya prescribing information, in collaboration with health authorities, to increase vigilance for PML," Novartis said in a statement.
The FDA has been notified of the third case.
Patients taking Gilenya are being urged to contact their healthcare professionals immediately if they experience symptoms such as new or worsening weakness; increased trouble using their arms or legs; or changes in thinking, eyesight, strength, or balance. Healthcare professionals should stop treatment and perform a diagnostic evaluation if PML is suspected.
Novartis said that with more than 125,000 patients having been treated with Gilenya and 240,000 patient years of exposure in both clinical trials and postmarketing setting, they continue to "stand behind the positive benefit-risk profile" of the drug in relapsing MS.
Source: Medscape Multispeciality Copyright © 1994-2015 by WebMD LLC (19/08/15)
Team finds early inflammatory response paralyses T cells (19/08/15)
In a discovery that is likely to rewrite immunology text books, researchers at UC Davis have found that early exposure to inflammatory cytokines, such as interleukin 2, can "paralyse" CD4 T cells, immune components that help orchestrate the body's response to pathogens and other invaders.
This mechanism may act as a firewall, shutting down the immune response before it gets out of hand. However, from a clinical standpoint, this discovery could lead to more effective cancer immunotherapies, better drugs for autoimmune conditions such as multiple sclerosis and new ways to expedite recovery from sepsis. The research, online July 28, appears in today's print edition of the journal Immunity.
"There's a three-signal process to activate T cells of which each component is essential for proper activation," said first author Gail Sckisel, a post-doctoral fellow. "But no one had really looked at what happens if they are delivered out of sequence. If the third signal - cytokines - is given prematurely, it basically paralyzes CD4 T cells."
To be activated, T cells must first recognize an antigen, receive appropriate costimulatory signals, and then encounter inflammatory cytokines to expand the immune response. Until now, no one realized that sending the third signal early - as is done with some immunotherapies - could actually hamper overall immunity.
"These stimulatory immunotherapies are designed to activate the immune system," said Sckisel, "but considering how T cells respond, that approach could damage a patient's ability to fight off pathogens. While immunotherapies might fight cancer, they may also open the door to opportunistic infections."
This was shown in mice which, after receiving systemic immunotherapy, had trouble mounting a primary T-cell response. The finding was confirmed in samples from patients receiving high-dose interleukin 2 therapy to treat metastatic melanoma.
"We need to be very careful because immunotherapy could be generating both short-term gain and long-term loss," noted lead author William Murphy, professor and acting chair in the UC Davis Department of Dermatology. "The patients who were receiving immunotherapy were totally shut down, which shows how profoundly we were suppressing the immune system."
In addition to illuminating how T cells respond to cancer immunotherapy, the study also provides insights into autoimmune disorders. The researchers believe this CD4 paralysis mechanism could play a role in preventing autoimmunity, a hypothesis they supported by testing immunotherapy in a multiple sclerosis model.
By shutting down CD4 T cells, immune stimulation prevented an autoimmune response. This offers the potential to paralyze the immune system to prevent autoimmunity or modulate it to accept transplanted cells or entire organs.
"Transplant patients go on immunosuppressants for the rest of their lives, but if we could safely induce paralysis just prior to surgery, it's possible that patients could develop tolerance," said Sckisel.
CD4 paralysis may also be co-opted by pathogens, such as HIV, which could use this chronic inflammation response to disable the immune system.
"This really highlights the importance of CD4 T cells," said Murphy. "The fact that they're regulated and suppressed means they are definitely the orchestrators we need to take into account. It also shows how smart HIV is. The virus has been telling us CD4 T cells are critical because that's what it attacks."
The team's next step is to continue this research in older mice. Age can bring a measurable loss in immune function, and inflammation may play a role in that process.
"For elderly people who have flu or pneumonia, their immune systems are activated, but maybe they can't fight anything else," said Murphy. "This could change how we treat people who are very sick. If we can block pathways that suppress the immune response, we may be able to better fight infection."
Source: Medicalxpress © Medical Xpress 2011 - 2015, Science X network (19/08/15)
Study highlights possible role of glial brain cells in neurological conditions (18/08/15)
Every brain cell has a nucleus, or a central command station. Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease. The study, published in the journal Nature Neuroscience, was partially funded by the National Institutes of Health (NIH).
“Unexpectedly we may have discovered a hidden pathway to understanding how astrocytes respond to injury and control brain processes. The pathway may be common to many brain diseases and we’re just starting to follow it,” said Katerina Akassoglou, Ph.D., a senior investigator at the Gladstone Institute for Neurological Disease, a professor of neurology at the University of California, San Francisco, and a senior author of the study.
Some neurological disorders are associated with higher than normal brain levels of the growth factor TGF-beta, including Alzheimer's disease and brain injury. Previous studies found that after brain injury, astrocytes produce greater amounts of p75 neurotrophin receptor (p75NTR), a protein that helps cells detect growth factors. The cells also react to TGF-beta by changing their shapes and secreting proteins that alter neuronal activity.
Dr. Akassoglou’s lab showed that eliminating the p75NTR gene prevented hydrocephalus in mice genetically engineered to have astrocytes that produce higher levels of TGF-beta. Hydrocephalus is a disorder that fills the brain with excess cerebral spinal fluid. Eliminating the p75NTR gene also prevented astrocytes in the brains of the mice from forming scars after injuries and restored gamma oscillations, which are patterns of neuronal activity associated with learning and memory.
The cell nucleus is a ball of chromosomes wrapped in a protective fatty membrane. In this study, the researchers discovered that treating astrocytes with TGF-beta freed a small piece of the p75NTR protein to bind to nucleoporins, a group of proteins that regulates the passage of molecules in and out of the nucleus. Their results suggest that binding enhances the flow of certain critical molecules into the nucleus and enables astrocytes to enter a reactive state.
“This research highlights the importance of the nuclear pore complex in the brain and raises the possibility that it may be a target for treating a wide range of neurological disorders,” said Jill Morris, Ph.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).
The scientists used high-resolution microscopes to watch the astrocyte nucleus in action. Nuclear pores that did not have the p75NTR gene were slightly larger than normal. When the scientists treated astrocytes with TGF-beta, they saw p75NTR proteins bind to nucleoporins and open the pores. This allowed transport into the nucleus of a protein called Smad2, which is essential for TGF-beta to exert its effects on astrocytes. In other experiments, the scientists showed that eliminating p75NTR from astrocytes blocked the transport of Smad2 into the nucleus.
“Nuclear pores are gatekeepers and p75NTR appears to be the key to unlocking particular gates,” said Dr. Akassoglou. “We discovered novel roles for both players and will continue to study how the nuclear pore complex controls neuronal development and disease.”
Source: National Institutes of Health (NIH) (18/08/15)
Further evidence of vitamin D role in MS found (13/08/15)
Researchers have conducted a survey of over 2,000 adults with multiple sclerosis to determine whether vitamin D supplementation, latitude and/or sun exposure are related to the relapse rate and disease progression of multiple sclerosis (MS).
Clinical trials have recently suggested vitamin D supplementation has a positive effect on MS. However, the dosage that provides the most benefits remains unclear. Thus, researchers recently assessed the relationship between different doses of vitamin D and health outcomes of MS. In addition, the researchers looked at latitude and sun exposure.
The researchers surveyed 2,301 participates with MS online. The average age was 45. The survey consisted of 163 questions inquiring about socio-demographics, MS diagnosis, level of disability, health related quality of life and symptom severity. They also asked specific questions regarding vitamin D supplementation dosage and sun exposure habits. The researchers found:
• A total of 1,504 (63 per cent) of participants reported they intentionally received sun exposure to increase their vitamin D status.
• The majority of participants took vitamin D supplements (81.8 per cent) with an average supplementation regimen between 2000 and 5000 IU daily.
• Deliberate sun exposure and latitude was strongly associated with health related quality of life. Although this relationship disappeared after adjusting for confounding factors.
• Vitamin D supplementation and health related quality of life were significantly related before and after adjusting for confounding factors with a dose-response effect.
• An increase of latitude by one degree (further from the equator) was associated with a two per cent increase in odds of moderate disability and a three per cent increase in odds of high disability compared to those with no disability or mild disability.
• Relapse rate was also related to latitude. An increase of latitude by one degree was associated with a one per cent increase in odds of having more relapses over the previous year.
• Those taking vitamin D supplements had about a one third lower annualised relapse rate compared to those who did not.
The researchers concluded: “We detected significant associations between latitude, deliberate sun exposure and vitamin D supplementation and health outcomes of this large group of people with MS.
“Vitamin D is likely to have a pivotal role in these associations; its role in MS health outcomes urgently requires detailed exploration with well-designed clinical trials.”
These findings provide further support to the extensive research that has found vitamin D plays a role in multiple sclerosis. The high percentage of MS patients who take vitamin D illustrates that MS patients have become aware of the benefits of vitamin D.
There are a few limitations to keep in mind in regards to this study. All measures were self-reported, leaving room for recall bias. Also, vitamin D status was not measured. Lastly, the study is cross-sectional, meaning that we cannot conclude causation.
Source: Vitamin D Council © Vitamin D Council 2015 (13/08/15)
Study finds exercise beneficial for children with MS (13/08/15)
Children with multiple sclerosis (MS) who engage in regular exercise may potentially have a milder form of the condition with fewer symptoms, according to results of a new study published in the journal, Neurology.
“Up to three-quarters of children with MS experience depression, tiredness, or memory and thinking impairment,” said lead author E. Ann Yeh, MD, of The Hospital for Sick Children (SickKids) in Toronto and Associate Professor at the University of Toronto in Toronto, Canada. “Our research is important since little is known regarding how lifestyle behaviours may affect MS.”
This area is of particular interest to neurologists because children with MS generally experience a more severe course compared to adults, developing more relapses leading to recurrent episodes of weakness. As a result, any intervention to improve quality of life for children with MS would represent a step forward.
MS is rare in children compared to adults, making up between 2-10 per cent of all patients with MS, typically occurring episodically in a so-called “relapsing and remitting” form.
The investigators in this study studied a total of 110 patients from the ages of 5-18. They provided questionnaires to 31 children with MS, inquiring about tiredness, depression and how often they engaged in exercise. They also evaluated 79 children who had experienced a single inflammatory neurologic episode as well. Sixty of the 79 patients also underwent MRI brain scans to evaluate brain volume and to characterize their particular MS lesions.
Based on the study data, just 45 per cent of the children with MS reported participating in any strenuous physical activity while 82 per cent of the other children participated in strenuous physical exercise.
Compared to the children with MS who did not engage in strenuous activity, those children with MS who did participate in strenuous physical activity were more apt to have a lower density of brain lesions that are a marker for disease activity, otherwise known as T2 lesions.
Those who did strenuous activity had a median of 0.46 cm3 of T2 lesions, compared to 3.4 cm3 for those with no strenuous activity. Also, those with strenuous activity had a median of 0.5 relapses per year, compared to 1 per year for those with no strenuous activity.
The take home message is that children who engaged in strenuous activity had fewer relapses and lower lesion volumes on MRI, ultimately reflecting a lower disease burden.
Children with MS in this study were also noted to have greater depressive symptoms and fatigue compared with the other children evaluated. Whole brain volumes revealed no differences in those with MS and those without the disease, with the results revealing no differences after researchers adjusted for the severity of the children’s disease.
Yeh emphasized that her study only revealed an association between level of physical activity and disease severity in MS, not a cause and effect relationship. In other words, it’s not clear if children with a milder form of disease are able to exercise more, or if exercise itself reduces the severity of the disease.
“These findings add to the possibility that physical activity may have a beneficial effect on the health of the brain,” explained Yeh.
“This is an excellent article,” said Dr. Paul Wright, Chair of Neurology at North Shore University Hospital in Manhasset, NY and Long Island Jewish Medical Center in New Hyde Park, NY, “that shows physical activity in children with multiple sclerosis and demyelinating disease is beneficial.”
“In this day and age where we are looking for the ‘medical edge’ for disease reduction and prevention, a simple approach of routine strenuous physical activity should be one of the arrows in our quiver for disease management,” explained Wright. In fact, “We would be very impressed, as physicians, if we developed a new medication that provided us with this study’s results,” offered Wright, adding “Physician’s treating paediatric multiple sclerosis may need to adopt a new approach to their patients.”
“It may be difficult to exercise with fatigue and depression; however, it appears that this is exactly what is needed,” concluded Wright.
That said, potential barriers continue to exist in implementing exercise programs among neurologists who currently care for children with MS.
“The main barrier,” explained Yeh, “is that formal exercise programs are hard to fit into the everyday lives of children when they are busy with activities.” “Lifestyle changes are really hard to implement and sustain without support, and there may be issues related to perception of disability despite no clear motor disability that may keep children with MS from choosing to be more physically active.”
One interesting question raised by this study is whether there might be a benefit to considering the use of antidepressants earlier in children with MS and depressive symptoms in order to evaluate if there might be improvement in mood followed by exercise capacity and strength. This could be further validated by a reduction in lesions seen on MRI.
While Yeh admits that her research did not address this type of intervention, “what I can say is that if there is an issue with clinically significant depression, children should be assessed by a physician and appropriate therapy should be initiated if needed. A different type of study would be required to determine the potential impact of prescribing antidepressants in this way.”
Overall, Yeh explains that her study “suggests that there may be a relationship between high levels of physical activity or strenuous activity and disease activity in children with MS.”
“There is a need for further longitudinal studies focusing on these issues, and furthermore, for interventional studies that evaluate practical ways of increasing physical activity in children,” she concluded.
Source: Forbes © 2015 PARS International Corp (13/08/15)
New multiple sclerosis testing model can predict if condition will intensify (10/08/15)
A new study, Joint Assessment Of Dependent Discrete Disease State Processes published, in the journal Statistical Methods in Medical Research has revealed a new method to determine the condition’s course in multiple sclerosis (MS) patients. The study was conducted by researchers at the Brigham Young University, Brigham and Women’s Hospital and Massachusetts General Hospital.
“The goal all along has been to develop personalised transition probabilities with regard to where they are in the disease process and where they’re most likely to go in the near future,” said the study’s lead author Dr. David Engler in a news release.
MS patients usually visit their doctors every six months. In these follow-up visits, their disability level is assessed, namely through the expanded disability severity scale score and relapse state. In the newly developed model, a doctor would simply introduce the patient’s data on relapse and disability score of the last two follow-up visits, plus some demographic data concerning the patient. The data is collected from the patient by his or doctor in a two-step process: first, patients indicate if they suffered a relapse since their last doctor visit. If so, patients then rate the intensity of the relapse symptoms on a 21-point scale (0, 0.5, 1.0 … 9.0, 9.5, 10). This information is then entered into the testing model.
The model, based on the information provided, will then determine the odds that MS will evolve to a milder stage, progress to a more aggressive stage, or maintain its stage for the next six months until the next follow-up visit.
“If the model suggests you are likely to be in a more debilitated state six months from now, your doctor might recommend a more rigorous treatment regime,” explained Dr. Engler.
This model is also helpful in reducing fears in MS patients. Alison Wadsworth received an MS diagnosis 25 years ago and has continued a very active life. According to her, the information she received from literature after the diagnosis reflected very negative future perspectives. “I would have loved knowing that there are many of us that manage to lead an almost-normal life with diet and exercise and lifestyle changes rather than becoming dependent on medicine that is very expensive,” said Wadsworth.
The model was tested in a cohort of 1,123 MS patients in Boston and found to be well-suited to evaluate disease course, and for the identification of predictors of a transition between the MS relapse-remitting phase of the disease and the secondary progressive phase.
“This is important because currently, the majority of MS treatments are effective in preventing new relapses, however to date, most of these therapies have shown little impact on overall disease progression,” noted the study’s co-author Dr. Tanuja Chitnis. “This tool may help to identify new treatments which improve overall disability measures.”
Dr. Engler and the study’s co-author Dr. Brian Healy have published several studies on MS. “As with anyone publishing medical literature, you hope that what you find makes a difference out there,” concluded Dr. Engler. “Every day, there are new medical findings, and you hope that proven methods are implemented.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (10/08/15)
Comorbidities linked to MS pain and fatigue (07/08/15)
Patients with multiple sclerosis (MS) who also have comorbidities, such as fibromyalgia and irritable bowel syndrome (IBS), are more likely to report severe pain and moderate-to-severe fatigue, according to a new study.
Researchers say comorbidities can affect the management of MS and reduce quality of life, and existing data shows an increased prevalence of fatigue and pain in MS. Little is currently known, however, about how these symptoms might be affected by comorbidities. To that end, the investigators enrolled 949 people with definite MS to examine the relationship between comorbidity, pain and fatigue. The patients were seen in four outpatient MS clinics in Canada, between July 2010 and March 2011.
“Closer examination of the associations between pain, fatigue and comorbidity may offer guidance for better management of these disabling symptoms in persons with MS,” said study author Kirsten Fiest, PhD, a postdoctoral fellow at the University of Manitoba, in Winnipeg.
Patients completed a comorbidity questionnaire, the Fatigue Impact Scale for Daily Use and the Health Utilities Index, which identifies patients with and without pain that disrupts daily life. There were two follow-up consecutive annual clinic visits, which examined the presence and severity of pain and fatigue and whether these symptoms improved, stayed the same or worsened.
The most common comorbidities at baseline were depression (29 per cent), hypertension (17.8 per cent), migraine (17.3 per cent), high cholesterol (12.4 per cent), anxiety (11.5 per cent), chronic obstructive pulmonary disease (COPD; 9.8 per cent) and IBS (7.9 per cent).
The researchers found that patients with fibromyalgia as a comorbidity were 3.74 times more likely to develop disruptive pain and 2.75 times more likely to report fatigue than people without this comorbidity. Patients with IBS were 2.21 and 1.7 times more likely to report disabling pain and fatigue than people without comorbid IBS.
At baseline, fatigue and pain were present in 53.4 per cent and 40.4 per cent patients. At the one-year follow-up, 32.7 per cent of the patients who did not have pain at baseline had incident pain; overall, 59.9 per cent of patients had pain by the end of the first year. By the second year, 35.2 per cent of patients without pain at baseline or the first year had incident pain, and 78.3 per cent of patients had pain.
The rates of incident fatigue at the one- and two-year follow-ups were 28.9 per cent and 29.9 per cent, respectively; 66.87 per cent of patients had fatigue by the end of the first year and 76.78 per cent had fatigue by the end of two years.
Patients with comorbid fibromyalgia had the greatest odds of having disabling pain and moderate to severe fatigue between baseline and the two-year follow-up (odds ratio [OR], 3.74 and 2.74, respectively). The ORs for comorbid IBS were 2.21 and 1.70, respectively, and were 1.58 and 2.68, respectively, for comorbid depression. Anxiety, COPD and autoimmune thyroid disease were also associated with significantly elevated odds for disabling pain and moderate to severe fatigue over time. The investigators did not calculate the ORs for incident pain for the first and second years among patients with various comorbidities because of small subgroup sizes without pain at baseline.
“Having pain management physicians be aware that other diseases that are potentially treatable seem to associate with pain in the multiple sclerosis population is important,” said Erik Charlson, MD, a fellow in MS at New York University Langone Medical Center, in New York City.
Dr. Charlson, who was not involved in the study, said these results fit a lot of the patients seen in his MS clinic.
“They have pain [and] depression; they may have another neurologic condition; they may have other difficult-to-manage problems that make for a huge problem to try to tease out what issues to treat,” he said.
Source: Pain Medicine News Copyright © 2004 - 2015 McMahon Publishing (07/08/15)
High-salt diet linked to multiple sclerosis (06/08/15)
New research has found diets high in sodium boost the risk of developing of multiple sclerosis.
Scientists with the University of Vermont in Burlington determined that salt influences immune cells that cause the disease, suggesting it may be one of the many environmental factors contributing to MS.
The findings, published in Federation of American Societies for Experimental Biology’s FASEB Journal, add to the growing body of evidence that suggests clear connection between certain foods interact with genetics and the human immune system to combat — or contribute to — disease.
"We hope to provide a comprehensive understanding of how and why environmental factors interact with individuals' unique genetic make up to influence autoimmune diseases such as MS," said Dimitry N. Krementsov, a researcher involved in the work from the University’s Department of Medicine, Immunobiology Program.
For the study, Krementsov and colleagues fed a high-salt diet to a mice and compared them to those fed a standard diet. They then induced a disease in these mice that mimics human MS. The result showed the mice fed a high-salt diet had worse clinical signs of the disease than those consuming a regular diet.
"As is the case with other things, you need to get enough salt so your body functions properly, but not too much or things start to go haywire," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "This report helps shed light on what can go wrong in individuals with genes that make one susceptible to autoimmune disease. It also helps us understand how much salt is just right for any given individual."
Source: NewsmaxMedia © 2015 Newsmax Media, Inc (06/08/15)
FDA issues PML warning for MS patients taking Gilenya (05/08/15)
Following reports of progressive multifocal leukoencephalopathy among patients taking Gilenya for multiple sclerosis, the FDA has issued a warning of possible infection for those prescribed the immunosuppressant drug.
Gilenya (fingolimod, Novartis) is an immunomodulator used to treat patients with relapsing forms of multiple sclerosis (MS). In 2013, a patient was reported to have developed progressive multifocal leukoencephalopathy (PML) after taking the drug; however, no conclusive link could be made due to previous treatment with multiple courses of IV corticosteroids and another immunosuppressant drug known to cause the infection.
Recently, the FDA was notified by Novartis of two more PML cases, one probable and one confirmed. The patient with probable PML was asymptomatic, but was diagnosed based on MRI results and the detection of JC virus in cerebrospinal fluid. The other patient was diagnosed based on clinical symptoms, MRI and virus detection.
The FDA recommends patients taking fingolimod and are experiencing symptoms to contact a health care professional immediately, and those prescribing the drug to stop treatment if PML is suspected. In addition, information about the two recent cases is being added to the drug label.
Source: Healio © 2015 (05/08/15)
Government expected to advise vitamin D boost (03/08/15)
Britons do not get enough sunlight leading to deficiencies of vitamin D and a host of related illnesses, research claims.
The vitamin – linked by some with combating cancer, multiple sclerosis, asthma and Type 2 diabetes – is formed naturally in the skin when it is exposed to sunlight.
Now for the first time government health advisers are expected to recommend that everyone should increase their daily intake of vitamin D with supplements because gloomy winters fail to provide enough sunshine to maintain healthy levels throughout the year.
Britons need to top up on their vitamin D artificially, according to a draft report published by the Scientific Advisory Committee on Nutrition (SACN). Until now, it was assumed that exposure to sunlight would enable most people to reach this target – but new scientific evidence suggests that is not the case in UK.
Links have also been drawn between vitamin D and the prevention of cancer, multiple sclerosis, asthma, and Type 2 diabetes – though these remain inconclusive. The report suggests people between 11 and 64 should ensure they have 10 micrograms of vitamin D every day.
But the report estimates that most people get only five micrograms from their diets. Dr Adrian Martineau, an expert on vitamin D at Barts and the London School of Medicine and Dentistry, said that a daily intake of 10 micrograms would “significantly improve public health in the UK”.
And he stressed that the latest advice marked a “sea change” in thinking. He said: “Before this the assumption was that adults were able to make all the vitamin D they needed from sunshine, and didn’t need to have any dietary or supplementary intake.
“The action of sunlight on the skin in the UK is highly variable depending on the time of year and the latitude – you’ll get more UVB [ultraviolet] in Brighton than in John O’Groats – and how much skin is exposed and the colour of skin.”
Nutrition experts said that most diets were not likely to provide the recommended 10 micrograms of vitamin D every day either. Helena Gibson-Moore, a scientist at the British Nutrition Foundation, said: “Given current intake levels of vitamin D from foods at less than five micrograms per day, the draft recommendation of 10 micrograms is unlikely to be achievable from these foods alone.”
She added: “Taking some exercise in the sunshine is sound advice for all.”
Professor Hilary Powers, chair of the SACN vitamin D working group, said: “It is important to remember that this vitamin D report is a draft so the recommendations may change after the consultation period.
“SACN will be publishing its final recommendations in early 2016.”
Source: Daily Express Copyright ©2015 Northern and Shell Media Publications (03/08/15)