Biogen's in the doghouse

"Are they surprised? I assume it will be water of a duck's back; Pharma rarely show remorse."

Multiple Sclerosis Research: BG-12 Phase III Results: it is ...

18 Jun 2013

Objectives & Methods: To investigate the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in MSer subgroups stratified according to baseline demographic and disease characteristics including ...

http://multiple-sclerosis-research.blogspot.com/

Multiple Sclerosis Research: Biogen Idec delays BG12 launch in ...

03 Jun 2013

PMLive. Biogen Idec says Tecfidera launch delayed in Europe. 31 May 2013 MSers in Europe who are eager to start Biogen Idec's new oral treatment Dimethyl Fumarate (Tecfidera) will now have to wait until the second half ...

http://multiple-sclerosis-research.blogspot.com/

Multiple Sclerosis Research: Biogen-Idec submits application to ...

22 May 2013

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 ...

http://multiple-sclerosis-research.blogspot.com/

Multiple Sclerosis Research: Biogen-Idec's response to homemade ...

19 Apr 2013

Biogen Idec recognizes that traditional pharmacy compounding can play a useful role in personalizing treatment for an individual patient. However, this should be done by licensed pharmacists who are trained and equipped ...

http://multiple-sclerosis-research.blogspot.com/

Smoking..Still time to Stop!

What can we do to get MSers to stop smoking? #MSBlog #MSResearch

Epub: Manouchehrinia A, Tench CR, Maxted J, Bibani RH, Britton J, Constantinescu CS. Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study. Brain. 2013 Jun 11.

Tobacco smoking has been linked to an increased risk of multiple sclerosis. However, to date, results from the few studies on the impact of smoking on the progression of disability are conflicting. The aim of this study was to investigate the effects of smoking on disability progression and disease severity in a cohort of patients with clinically definite multiple sclerosis. We analysed data from 895 patients (270 male, 625 female), mean age 49 years with mean disease duration 17 years. Forty-nine per cent of the patients were regular smokers at the time of disease onset or at diagnosis (ever-smokers). Average disease severity as measured by multiple sclerosis severity score was greater in ever-smokers, by 0.68 (95% confidence interval: 0.36-1.01). The risk of reaching Expanded Disability Status Scale score milestones of 4 and 6 in ever-smokers compared to never-smokers was 1.34 (95% confidence interval: 1.12-1.60) and 1.25 (95% confidence interval: 1.02-1.51) respectively. Current smokers showed 1.64 (95% confidence interval: 1.33-2.02) and 1.49 (95% confidence interval: 1.18-1.86) times higher risk of reaching Expanded Disability Status Scale scores 4 and 6 compared with non-smokers. Ex-smokers who stopped smoking either before or after the onset of the disease had a significantly lower risk of reaching Expanded Disability Status Scale scores 4 (hazard ratio: 0.65, confidence interval: 0.50-0.83) and 6 (hazard ratio: 0.69, confidence interval: 0.53-0.90) than current smokers, and there was no significant difference between ex-smokers and non-smokers in terms of time to Expanded Disability Status Scale scores 4 or 6. Our data suggest that regular smoking is associated with more severe disease and faster disability progression. In addition, smoking cessation, whether before or after onset of the disease, is associated with a slower progression of disability.

The evidence against smoking is mounting. It is well established that smoking increases the risk of MS (n.b. this is not the same as saying that smoking causes MS). The evidence regarding smoking and disease progression has previously been less rigorous. This study demonstrates that smokers reach disease milestones more rapidly than non-smokers. Interestingly, people who stop smoking (even after diagnosis) appear to have slightly slower disease progression; their disease behaves more like that of a non-smoker.

We don't know why this is. One theory as to why smoking affects MS is that there is some evidence of a biological interaction between smoking and EBV, as nicotine metabolism has a shared pathway with EBV activation. But this is all speculation - nothing has been conclusively demonstrated. Whilst evidence of association and influence on MS grows, the why and how remain...

Anti viral antibodies in CSF

More evidence that viruses play a role in MS. #MSBlog #MSResearch

Epub: Virtanen et al. Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings. Mult Scler. 2013 May 30. 

BACKGROUND: Two human herpesviruses, human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV), have been repeatedly linked to multiple sclerosis (MS).

OBJECTIVE: The aim of this study was to investigate HHV-6 and EBV reactive oligoclonal bands (OCBs), and viral DNA in the intrathecal compartment in MS.

METHODS: The reactivity of OCBs in cerebrospinal fluid (CSF) for EBV and HHV-6 antigens and stability of virus reactive OCBs over time were studied in a well-characterized MS patient cohort. Associations between virus reactive OCBs and viral DNA in CSF (and any clinical and/or radiological findings) were investigated.

RESULTS: Of patients with MS, 38% had OCBs reactive to either one of the viruses studied, compared to none in the patients with other inflammatory neurological diseases (p=0.005). The banding pattern of virus reactive OCBs remained the same over time. Furthermore, MS patients with viral DNA in CSF had more contrast enhancing lesions (CELs).

CONCLUSION: The stable presence of herpesvirus reactive OCBs in CSF further strengthens the association of MS with these viruses. The finding that herpesviruses might be linked to the appearance of active lesions warrants investigation of new therapeutic strategies to treat these viruses in MS.

In MSers there is more evidence that people with antibodies in the brain fluid react with viruses more than non-MSers. However, some oligoclonal bands do not react to EBV or HHV6 in 62% of time So is this evidence for a viral role for MS and go the Charcot Project or is it something else?

More MS genes found

What has the genome still have to hide? #MSBlog #MSResearch

Epub: International Multiple Sclerosis Genetics Consortium Network-Based Multiple Sclerosis Pathway Analysis with GWAS Data from 15,000 Cases and 30,000 Controls. Am J Hum Genet. 2013 May 22.

Multiple sclerosis (MS) is an inflammatory CNS disease with a substantial genetic component, originally mapped to only the human leucocyte antigen (HLA) region (Transplantion=DNA fingerprinting antigen). In the last 5 years, a total of seven genome-wide association studies and one meta-analysis successfully identified 57 non-HLA susceptibility loci. Here, we merged nominal statistical evidence of association and physical evidence of interaction to conduct a protein-interaction-network-based pathway analysis (PINBPA) on two large genetic MS studies comprising a total of 15,317 cases and 29,529 controls. The distribution of nominally significant (marginally important) loci (genes) at the gene level matched the patterns of extended linkage disequilibrium (inherited together more often than would occur by chance) in regions of interest. We found that products of genome-wide significantly associated genes are more likely to interact physically and belong to the same or related pathways. We next searched for subnetworks (modules) of genes (and their encoded proteins) enriched with nominally associated loci within each study and identified those modules in common between the two studies. We demonstrate that these modules are more likely to contain genes with bona fide susceptibility variants and, in addition, identify several high-confidence candidates (including BCL10, CD48, REL, TRAF3, and TEC). PINBPA is a powerful approach to gaining further insights into the biology of associated genes and to prioritizing candidates for subsequent genetic studies of complex traits.

Gene hunters think that some genes that control susceptibility to MS work together in networks abit like you need elven players, some substitutes, a manager and fans to make a football team, Looking at networks they are finding more candiadate genes.

Guest post: gray matter lesions in MS

Gray matter lesions in MS. Part of the iceberg we haven't been able to see. #MSBog #MSResearch

"Some of you may already know that we have joined UCL Partners an umbrella organisation that covers academic and clinical services in Central and Northeast London. This is the first of many guest posts from one of the researchers at UCL as part of our partnership."

"These MRI images are simply stunning and begin to give you an idea what lies behind MS-related cognitive impairment and why MS is like an iceberg. We are only jut beginning to see the extent of the gray matter pathology in life."

Dr Varun Sethi works as a clinical research associate at the Department of Neuroinflammation, UCL Institute of Neurology. His area of research is the study of grey matter lesions in MSers, using MRI. He trained as a doctor in India and after his postgraduate degree in Medicine, came to UK initially for a Masters in Clinical Neurology and is currently working towards his PhD. 

Grey matter lesions in MS

It is often thought that brain changes in people with multiple sclerosis (MS) are mostly limited to white matter (found in the centre of the brain, and containing nerve fibre bundles that are wrapped in myelin), and seeing white matter spots (lesions where the myelin has been removed) using magnetic resonance imaging (MRI) has been an important part of the investigations that help diagnose MS. However, recent work has shown that grey matter (found mostly on the outer edges of the brain, and containing nerve cells) is also affected by MS, and lesions occur there too, but are difficult to see on standard MRI scans.

Knowing that MS lesions occur in grey matter, but that they are difficult to see using standard MRI scans, different methods have been studied to improve this. One such method - Double Inversion Recovery (DIR) - has proven particularly useful to detect grey matter lesion, and has helped us to study the effects grey matter lesions have on people living with MS. However, with DIR, most grey matter lesions are still not seen, and so it is difficult to gain a true impression of how clinically important, or not, they are. In order to improve our understanding of grey matter lesions in MS, we used a previously developed MRI scan called Phase Sensitive Inversion Recovery (PSIR) to provide much more detailed scans of the brain. Using this, when compared with DIR we see about 2 to 3 times more grey matter lesions. We are now looking at whether or not this method improves our understanding of the relationship between grey matter lesions, physical and cognitive dysfunction. We will also be comparing these findings in patients with MS, with healthy controls and patients with other neurological conditions, to see if grey matter lesions can aid in the diagnosis of MS when it otherwise in doubt.

Disclosures: The NMR Research Unit is supported by the MS Society of Great Britain and Northern Ireland and the UCL UCLH Comprehensive Biomedical Research Centre; The MS Society of Great Britain and Northern Ireland has provided financial support for staff and research costs. V Sethi receives research support from Biogen Idec and Novartis. DT Chard receives research support from the Multiple Sclerosis Society of Great Britain and Northern Ireland and holds stock in GlaxoSmithKline and has received honararia for educational work and advisory board membership from Teva and Bayer.

Déjà vu: DMTs are simply too expensive

Déjà vu: MSologists are having the same problem as our colleagues in oncology with the price of DMTs. #MSBlog #MSResearch

Editorial. Sticker shock. Nature Medicine 19, 653 (2013) doi:10.1038/nm.3244 Published online 06 June 2013

.... A recent plea by oncologists condemning inflated prices for some cancer drugs has ignited a debate on this topic between clinicians and pharmaceutical companies and highlights the need for a broader assessment of drug valuation.....

...... In a recent commentary published in the journal Blood, an international group of more than 100 clinicians and scientists criticized pharmaceutical companies that market costly cancer drugs to treat chronic myeloid leukemia (CML). The authors argued that the prices of six CML drugs have reached unsustainable levels that jeopardize patients' treatments and economic well-being.....

"I have heard similar mutterings from US colleagues."

.....The article has sparked reactions that underscore the complexity of the issue, which encompasses questions of how drug values are determined, where moral boundaries are drawn and what mechanisms can be employed to reduce the divide between commercial interests and patient welfare.....

.... In response to this disparity, some regulatory agencies and insurance companies have refused to approve payment for certain high-cost treatments. In the UK, the National Institute for Health and Care Excellence (NICE) evaluates the cost-effectiveness of drugs that have been approved by the European Medicines Agency (EMA) and issues funding guidance to the National Health Service (NHS). The NHS covers the cost of drugs that NICE approves for a given disease...

..... In the US, medical insurance companies have also refused to reimburse patients for some cancer drugs....

..... Medical expenses are the most frequent cause of personal bankruptcy in the US, and the high cost of drugs is a factor in poor adherence and treatment failure..... 

..... Ultimately, legislation that would allow healthcare agencies to negotiate directly with drug companies or that would cap drug prices might be needed to curtail further cost escalation of cancer treatments. Pharmaceutical companies realize that not everyone can pay for their drugs and have created patient assistance programs, some of them benefiting underdeveloped countries or underprivileged segments of the population.....

 Click here for the full article

"The issue of expensive DMTs has been aired many times on this blog. It is interesting to see that it is not limited to our field. It is clear the status quo is unsustainable. What will be the outcome?"

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