Research

"In keeping with my current policy of uploading all of my presentations; the following are my slides that I used in my debate with Dr Brenner at the ABN is Glasgow. I managed to scrape home with a few swing voters; probably my staff who felt sorry for me." "I built up my arguments against the motion by using a fictitious, but quite real, case study. In essence this lady had active MS in that her MRI was very active with an increase in lesion load, gadolinium enhancing lesions and progressive brain atrophy. But as she did not have overt clinical relapses I was not able to escalate her treatment to either fingolimod of natalizumab under the current NICE guidance. I also used surveys I had done  to show that the majority of my colleagues in the UK don't use MRI to monitor MS disease activity and  neither do they use guidelines that incorporate MRI into decision-making algorithms regarding switching or escalating DMTs. Therefore on the balance of probabilities the... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

3X a week glatiramer acetate (Copaxone); innovation or life-cycle management? #MSBlog #MSResearch Epub: Khan et al. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol. 2013 May 20. doi: 10.1002/ana.23938. Objective: To assess the efficacy and safety of glatiramer acetate (GA) 40 mg administered three times weekly (tiw) compared with placebo in RRMSers.  Methods: This randomized, double-blind study was conducted in 142 sites in 17 countries. RRMSers with at least one documented relapse in the 12 months before screening, or at least two documented relapses in the 24 months before screening, and an Expanded Disability Status Scale score ≤5.5, were randomized 2:1 to receive either subcutaneous (sc) GA 40 mg tiw (1 mL) or placebo for 12 months.  Results: Of 1524 MSers screened, 1404 were randomized to receive GA 40 mg sc tiw (n=943) or placebo (n=461). Ninety-three percent and 91% of MSers in the placebo and GA groups, respectively,... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Epub: Mierzwa et al. FGF2 and FGFR1 Signaling Regulate Functional Recovery Following Cuprizone Demyelination Neurosci Lett. 2013. doi:pii: S0304-3940(13)00430-8. 10.1016/j.neulet.2013.05.010.  In demyelinating diseases, such as multiple sclerosis, remyelination offers the potential to recover function of viable denuded axons by restoring saltatory conduction and/or protecting from further damage. Mice with genetic reduction of fibroblast growth factor 2 (Fgf2) or Fgf receptor 1 (Fgfr1) exhibit dramatically improved remyelination following experimental demyelination with cuprizone. The current studies are the first to test neurobehavioral outcomes with these gene deletions that improved remyelination. The cuprizone protocols used did not produce overt abnormalities but did reduce bilateral sensorimotor coordination (complex wheel task) and increase sociability (two chamber apparatus with novel mouse). A significant effect of genotype was observed on the complex wheel... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Epub: Kinnunen et al. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Invest. 2013. doi:pii: 68775. 10.1172/JCI68775. Multiple sclerosis (MS) is a genetically mediated autoimmune disease of the central nervous system. B cells have recently emerged as major contributors to disease pathogenesis, but the mechanisms responsible for the loss of B cell tolerance in patients with MS are largely unknown. In healthy individuals, developing autoreactive B cells are removed from the repertoire at 2 tolerance checkpoints during early B cell development. Both of these central and peripheral B cell tolerance checkpoints are defective in patients with rheumatoid arthritis (RA) and type 1 diabetes (T1D). Here, we found that only the peripheral, but not the central, B cell tolerance checkpoint is defective in patients with MS. We show that this specific defect is accompanied by increased activation and homeostatic proliferation of mature naive B cells.... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Live MS Twitter Chat: Tuesday May 29th, 6pm UK Summer Time or 1 pm EST #HealthTalk #MSBlog "I have volunteered to do a Twitter Chat to honor World MS Day next week. This is a live Q&A session via Twitter. Although I tweet daily and use Twitter all the time this will be my first live event. You are welcome to sign in to and participate. To participate you will need your own Twitter account. To follow the Chatter it is best to use TweetChat (www.tweetchat.com), a site dedicated to live Twitter conversations, or TweetDeck (www.tweetdeck.com); both these sites allow you track conversations using the # (hashtag). Next Tuesday the hashtag that will be used is #HealthTalk" For more information check out the Healthtalk site:  In honor of World MS Day on May 29th, Everyday Health will co-host a live Twitter chat on Tuesday, May 28 at 6pm UK Summer Time or 1 pm EST, with experts from the National Multiple Sclerosis Society, plus other guests affiliated with the Society. Bruce... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Time to adapt; are online risk calculators going to change your practice? #MSBlog #MSResearch Heesen et al. Prognostic Risk Estimates of Patients with Multiple Sclerosis and Their Physicians: Comparison to an Online Analytical Risk Counseling Tool. PLoS One. 2013 May 17;8(5):e59042. Print 2013 BACKGROUND: Prognostic counseling in MS is difficult because of the high variability of disease progression. Simultaneously, MSers and physicians are increasingly confronted with making treatment decisions at an early stage, which requires taking individual prognoses into account to strike a good balance between benefits and harms of treatments. It is therefore important to understand how MSers and physicians estimate prognostic risk, and whether and how these estimates can be improved. An online analytical processing (OLAP) tool based on pooled data from placebo cohorts of clinical trials offers short-term prognostic estimates that can be used for individual risk counseling. OBJECTIVE: The... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

We have talked about the publishing process before, but the peer review process (work assessed by your fellow scientists) is not always straightforward and rejection of your work always hurts. If the comments are sensible you learn, adopt, adapt and move on, but if the comments are destructive compared to being constructive, it is annoying. This video gets the feeling across what it can be like if you are not happy with the reviewers comments (apologies if you speak German and can actually see the subtitles are not quite right). [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

I am sorry the "Rant of the Week" appeared yesterday. It was not meant to be (yet) and should not have been aired.......and was removed as soon as I realized it had been posted. To  paraphrase for those that read it, and to explain for those that did not read it or could not understand it.   "Sometimes there is a load of old rubbish (mushroom food) published in the scientific press. This type of information may not be reproducible and so lack importance". Prof G and I have been nominated for a Public Engagement Award to be announced Tomorrow. I hope this did not blow it with the Judges. I may explain the story more some day. Wrist suitably slapped. [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Epub: Tachibana et al. Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer. Cell. 2013 doi:pii: S0092-8674(13)00571-0. #MSResearch #MSBlog: Designer stem cells now a reality Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

In response to a comment The Green Cross Code Man? (Green Cross Code Man is Dave Prowse, the same guy that played Darth Vader in the original Star Wars Trilogy..Voice was James Earl Jones). or The Honey Monster? We receive nothing from Sugar Puffs or Quaker Emmmm.......Obviously some throwback from the Sixties [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Biogen Idec announced it has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for approval of peginterferon beta-1a, a pegylated subcutaneous injectable candidate for relapsing forms of MS.This regulatory submission was based on the results from the first year of the two-year global Phase 3 ADVANCE study. The data demonstrated that peginterferon beta-1a met all primary and secondary endpoints by significantly reducing disease activity including relapses, disability progression and brain lesions compared to placebo, and showed favorable safety and tolerability profiles at one year. In addition to the BLA filing with the FDA, Biogen Idec plans to submit a Marketing Authorisation Application (MAA) for peginterferon beta-1a to the European Medicines Agency (EMA) in the coming weeks.Peginterferon beta-1a is a new molecular entity in which interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body, enabling... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Do you suffer from pseudobulbar affect or emotional lability? #MSBlog #MSResearch "Pseudobulbar affect is a syndrome of emotion that comprises disinhibition, characterised by uncontrollable, exaggerated, and often inappropriate emotional outbursts, which may cause severe distress, embarrassment, and social dysfunction. MS is a common cause of a pseudobulbar affect and typically occurs in MSers with progressive disease that are disabled. The presence of pseudobulbar affect occurs when MS lesions involve the frontal lobes or a region in the brain stem called the pons. In a large online survey ~10% of MSers had pseudobulbar affect; this high figure indicates that the condition is under-recognised. This is important as there are effective treatments that can reduce the frequency and intensity of these emotional outbursts. If this affects you and has not been recognised, you may want to bring it to the attention of your neurologist or specialist nurse." Work et al. Pseudobulbar affect:... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Stress is associated with the appearance of active MS lesions on MRI. #MSBlog #MSResearch Epub: Burns et al. Do positive or negative stressful events predict the development of new brain lesions in people withmultiple sclerosis? Psychol Med. 2013:1-11. BACKGROUND: Stressful life events have long been suspected to contribute to MS disease activity. The few studies examining the relationship between stressful events and neuroimaging markers have been small and inconsistent. This study examined whether different types of stressful events and perceived stress could predict the development of brain lesions.  METHOD: This was a secondary analysis of 121 MSers followed for 48 weeks during a randomized controlled trial comparing stress management therapy for MS (SMT-MS) to a wait list control (WLC). MSers underwent MRI scans every 8 weeks. Every month, MSers completed an interview measure assessing stressful life events and self-report measures of perceived stress, anxiety and... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Research into MS prevention and treatment will receive a boost, with the Australian Government to invest a further $1 million to assist MSRA to continue its world class research over the next 4 years.

Research into multiple sclerosis (MS) prevention and treatment will receive a boost, with the Australian Government to invest a further $1 million to assist Multiple Sclerosis Research Australia (MSRA) to continue its world class research over the next 4 years.

'Every year around 1,000 Australians, mostly in their twenties to forties and disproportionately women, are diagnosed with MS,' the Health Minister Hon Tanya Plibersek MP said today.

"Our phenytoin in acute optic neuritis trial sponsored by the National MS Society has been running since Feb 2012. Despite cynics stating that we would not recruit very quickly things are going very well; we have now randomised 51 Optic Neurite-ers (ONers) to the study. We are confident that we will reach our target of 90 ONers before the end of the year." google.load('visualization', '1', {packages:['gauge']}); google.setOnLoadCallback(drawChart); function drawChart() { var data = google.visualization.arrayToDataTable([ ['Label', 'Value'], ['Screened', 103], ['Randomised', 51], ['Withdrawn', 2] ]); var options = { width: 660, height: 200, redFrom: 90, redTo: 120, yellowFrom:75, yellowTo: 90, minorTicks: 5 }; var chart = new google.visualization.Gauge(document.getElementById('chart_div')); chart.draw(data, options); ... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

There isn't any....Is this what you want?  Todays News....Nothing! Tomorrows News...Nothing! All month......Nothing! How many studies do you want Prof G to be doing at once? You can only spread yourself so much................. Who is helping getting CAMPATH through the Regulatory Process....? Its not your "Noble Prize Elect".....who's on leave for the Year. Doing trials are one thing, Coming up with the Idea in the first place is another and getting drugs to the Mser is yet another problem Timelines! DMTs; some recently approved in USA, and more on their way in Europe. In UK the price will be the major hurdle. When will drugs be available?...Ask the regulators and companies...we have no control on their pricing..which along with side effects and efficacy and your postcode will determine availability. Neuroprotectants....get on a trial if you can now! Closest to Market will be Fingolimod, that is if it works for Progression. The PPMS trial is fully... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

"Good news, we screened and entered our first MSer into the INSPIRE trial last week. This study is part of our Charcot Project that is testing the hypothesis that MS may be due to a virus. The following short video tells you about this initiative." Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis (INSPIRE) ClinicalTrials.gov identifier: NCT01767701 Detailed Description: There is accumulating research evidence that Human Endogenous Retrovirus (HERV) and herpes viruses (in particular Epstein-Barr Virus) are involved in the pathogenesis of multiple sclerosis. People with active MS have higher levels of HERVs than people either without MS or who have other neurological conditions. It has been shown that HERVs may produce neurotoxic proteins/antigens associated with MS activity and disease progression. This is the first clinical trial investigating the hypothesis that the antiretroviral drug raltegravir may suppress HERV activity and ameliorate progression of... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Austerity Britain and access to services in the NHS. #MSBlog #MSResearch Epub: Markwick et al.The perceptions of people with multiple sclerosis about the NHS provision of physiotherapy services Disabil Rehabil. 2013 May. Purpose: In 2008, the Royal College of Physicians (RCP) and MS Trust conducted a second audit of NHS services for people with MS (PwMS). Using the free text comments obtained from the RCP and MS Trust audit, this study aimed to perform content analysis on the views of PwMS about MS services, focussing on physiotherapy provision. Method: A total of 757 PwMS included a free text comment on MS services and an additional 41 commented separately about physiotherapy services. The data were analysed using content analysis, which identified three main themes, positive, negative and neutral and subsequent categories and sub-categories. Intra- and inter-rater reliability were assessed and the data were manipulated to address the research aim. Results: This study found that... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

Another one bites the dust. Pharma is an expensive and risky business. #MSBlog #MSResearch Vrinda Manocha. XenoPort to drop multiple sclerosis drug, shares fall. Reuters May 20, 2013 12:32pm EDT.  XenoPort will stop development of Arbaclofen placarbil an experimental MS treatment it hoped to launch in 2015 after a late-stage trial failed to show significant improvement over a placebo. Arbaclofen placarbil, which was intended to treat spasticity, stiffness and involuntary multiple spasms, was tested on 228 MSer in the United States. Dosages of 30 mg and 45 mg were administered twice a day. XenoPort said seven patients experienced adverse events, none of which were related to the treatment. XenoPort said on Monday that arbaclofen placarbil did not show statistical significance compared to the placebo on two clinical scales - severity of symptoms and response to treatment, and spasticity. The drug, arbaclofen placarbil, was XenoPort's only product in late-stage trial,... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]

MS cause destruction of tissue structure in children with MS. #MSBlog #MSResearch Epub: Blaschek et al. Early White Matter Changes in Childhood Multiple Sclerosis: A Diffusion Tensor Imaging Study. AJNR Am J Neuroradiol. 2013 May 16. BACKGROUND AND PURPOSE: Loss of integrity in nonlesional white matter occurs as a fundamental feature of MS in adults. The purpose of this study was to evaluate DTI-derived measures of white matter microstructure in children with MS compared with age- and sex-matched controls by using tract-based spatial statistics. DTI = diffusion tensor imaging; DTI allows the mapping of the diffusion process of molecules, mainly water, in the brain and spinal cord non-invasively. Molecular diffusion in tissues is not free, but reflects interactions with many obstacles, such as fibres, membranes, etc. Water molecule diffusion patterns can therefore reveal microscopic details about tissue architecture, either normal or in a diseased state. The unit that... [[ This is a content summary only. Visit my website for full links, other content, and more! ]]