Wednesday, 30 November 2011
We accept that your comments are not always going to be positive, but it helps if the comments are constructive when being negative.
CCSVI as monitored with Google Trends
"The Google trend data on CCSVI continues to show a downward trend. The majority of hits are still from Canada, Italy and Serbia; a very interesting regional social phenomenon."
"When the dust settles on CCSVI it will be worth a detailed analysis to see if we can learn any lessons to prevent this from happening again."
"Too much money, energy and most importantly human life has been wasted on this issue. Not to mention the impact it has had on the relationships between patients, patient advocates and healthcare professionals."
- 38 patients have died (21%); most of the deaths have occurred within approximately 2 months after PML diagnosis
- 143 patients are alive (79%), it is too early to draw conclusions about the outcomes of patients who develop PML while on natalizumab treatment.
"It is clear that Natalizumab is associated with a risk of getting PML that varies depending on JC viral status, previous exposure to other immunosuppressive drugs and duration of treatment. Knowing these risks will allow you and your neurologist to make an informed decision on what to do with your treatment."
"In my opinion, a defined risk is better than an undefined risk."
CoI: Multiple, please note that all the data in this post has been supplied by Biogen-Idec as part of their "monthly natalizumab safety update and PML risk stratification programme".
Please remember to register your interests for the Research Day, You can do this if you Click Here.
Can't wait to open the first window and we will give you hints of what's in store so remember to register
Tuesday, 29 November 2011
BACKGROUND AND PURPOSE: It is well known that patients with MS tend to have abnormal iron deposition in and around the MS plaques in the brain. In this study, we quantify iron content in patients with MS and healthy volunteers.
MATERIALS AND METHODS: Fifty-two patients with MS were recruited to assess abnormal iron content in brain structures involved in movement. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep grey matter structures.
RESULTS: A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor greater than three standard deviations from the normal mean (P < .05). Standard deviation is a measure of variability around a mean (average. middle point). 1.96 standard deviations would be expected contain 95% of the results and >3 standard deviations only less than 0.5% of results would be expected to occur at this level if it occured by chance. So the chance result would occur in 1 in a thousand times you do the experiment but would occur 650 times in a thousand (65%) so these results are unlikely to be a chance result. The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content.
CONCLUSIONS: Iron-weighting factors in the brain appeared to be abnormal in roughly two-thirds of patients with MS
OBJECTIVE: To compare brain atrophy rates in patients with long-standing benign MS vs typical early MS.
PATIENTS: 39 MS'ers with clinically defined benign MS and an age-matched group of 40 MS'ers with early RRMS.
RESULTS: The mean (SD) annualized brain atrophy rate in MS'ers with benign MS (-0.16% [0.51%]) was lower than that in patients with early MS (-0.46% [0.72%]) (P = .02). The difference remained significant after controlling for age, sex, and treatment (P = .04).
CONCLUSIONS: Serial magnetic resonance imaging revealed a low 2-year rate of brain atrophy in MS'ers with clinically benign MS, suggesting a less prominent degenerative component in its pathogenesis than in patients with typical early MS. Identification of patients with a low rate of brain atrophy may indicate a benign course.
Monday, 28 November 2011
A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With SPMS (ASCEND in SPMS)
- Ages Eligible for Study: 18 Years to 58 Years
- Genders Eligible for Study: Both
- Accepts Healthy Volunteers: No
Major Inclusion Criteria:
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Be between the ages of 18 and 58, inclusive, at the time of informed consent.
- SPMS defined as relapsing-remitting disease followed by progression of disability independent of or not explained by MS relapses for at least 2 years.
- EDSS score of 3.0 to 6.5, inclusive.
- MS Severity Score (MSSS) of 4 or higher.
- Documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide.
- RRMS or primary progressive MS as defined by the revised McDonald Committee criteria.
- Clinical relapse (within 3 months) prior to randomization.
- T25FW test of >30 seconds during the screening.
- Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils.
- Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment.
- Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed).
- History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study.
- History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
- Known history of or positive test result for Human Immunodeficiency Virus (HIV).
- Positive test result for hepatitis C virus (test for hepatitis C virus antibody [HCV Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).
- History of transplantation or any anti-rejection therapy.
- Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening.
- History of PML or other opportunistic infections.
- Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation.
- Any prior treatment with natalizumab.
- Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization.
- Treatment with IV or oral corticosteroids, intravenous immunoglobulin (IVIg), or plasmapheresis for treatment of MS within the 3 months prior to randomization.
- Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization.
- Treatment with 4-aminopyridine within 30 days prior to randomization, unless a stable dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study.
Sunday, 27 November 2011
"I don't find this result surprising given the current reputational issues Big Pharma have with the general public.However, I disagree with these results. If it wasn't for Big Pharma we wouldn't have DMTs for MS or the exciting pipeline that currently exists."
"MS'ers may be surprised but there are currently two PPMS and one SPMS trial recruiting sponsored by Big Pharma. The anti-Lingo trial that is targeting remyelination is also a Big Pharma project. All these have been profiled on this blog in the recent past."
"What is worrying however is the bad publicity "big money" brings to the field."
"It is also becoming increasingly difficult to get investigator trials sponsored, for example funding for a recent vitamin D trial was turned down in the UK. We are not sure why as the trial was well designed, the case for vitamin D is compelling and the study was powered to be definitive. May be next time?"
"We are about to submit a grant to test an anti-EBV drug in MS. Again the case is compelling for this trial. Let's hope the reviewers' and funders' think the same."
"I wonder if Danone and/or Nestle would be interested in funding a probiotic trial in MS? Please complete the new poll to let us know. You never know your response may be the beginning of a powerful lobby."
Saturday, 26 November 2011
If you are using a mobile blogger to view this post or email alerts please log-on via the web to complete the poll.
What are probiotics?
Probiotics are live microorganisms thought to be beneficial to the host organism. The currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host".
Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also be helpful. Probiotics are commonly consumed as part of fermented foods with specially added active live cultures; such as in yogurt, soy yogurt, or as dietary supplements.
(For more on probiotics please see Wikipedia entry)
"Who knows your vote may be the beginning of a new form of lobbying to get trials of this sort done in MS."
BACKGROUND: Certain intestinal microflora are thought to regulate the systemic immune response. Lactic acid bacteria are one of the most studied bacteria in terms of their beneficial effects on health and autoimmune diseases; one of which is MS. They investigated whether the lactic acid bacterium Pediococcus acidilactici, which comprises human commensal bacteria, has beneficial effects on experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
CONCLUSIONS: An orally administered single strain of P. acidilactici R037 ameliorates EAE by inducing regulatory cells. Their findings indicate the therapeutic potential of the oral administration of R037 for treating MS.
|Spinal cord lesion in NMO|
CONCLUSIONS.: The testing for NMO-IgG antibodies is important for distinguishing ON in NMO from multiple sclerosis in cases of ON refractory to steroid treatment. These cases suggest that testing for NMO-IgG antibodies should be performed in comparative trials on a larger series.
Friday, 25 November 2011
The objective of the study was to treat fatigue in MS'ers by a neurocognitive rehabilitation program aimed at improving motor planning by using motor imagery (MI). 20 MS'ers complaining of fatigue were treated for 5 weeks with exercises of neurocognitive rehabilitation twice a week. MS'ers were evaluated by Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MSQoL54, Expanded Disability Status Scale (EDSS), and MS Functional Composite (MSFC).
The mammalian nervous system is characterized by myelination, a fundamental biological process that protects the nerve processes of axons and facilitates the transmission of electrical pulses.
Purpose: Neurogenic detrusor overactivity (NDO. The muscle controlling bladder contraction is over active = urinary incontinence) is common in patients who suffer from multiple sclerosis (MS). When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A=Botox) injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS.
Materials and Methods: Seventy-one patients with MS underwent their first BTX-A injection for refractory (doesn't respond to therapy) NDO. They had bladder function assessed before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor), improvement, or total failure (urge incontinence and overactive detrusor = when you've gotta, you've gotta go).
BoTox Injection Sites
Results: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001), maximum vladder capacity (p = 0.0035), maximum detrusor pressure (p = 0.0000001). 46% of the patients were in the ″ full success ″ group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015).
Conclusions: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anti-cholinergic (inhibit acetyl choline that is a nerve transmitter chemical) drugs fail to reduce NDO.
More confirmatory evidence for the value of Botox...its not just about fixing foreheads but it can be a valuble medicine. Please leave a look at previous posts
Thursday, 24 November 2011
MouseDoc: "So when and why are you going to shut it down?"
Prof G: "I was having one of those days when I made the comment, but with the amazing response we've had, we've just got to keep it going!"
After G gets over another strenous week, we will digest your suggestions (thank you) and have a chat about how we juggle things.
So Happy Thanksgiving from Dr & Ms. Mouse (My American Other half) enjoy your Turkey (Nut Loaf for the Veggies) and see you over the weekend or next week!
Menge T, Lalive PH, von Budingen HC and Genain CP Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis. Journal of Neuroinflammation 2011, 8:161 (17 November 2011)
BACKGROUND:Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS.
METHODS:Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to MOG isoforms, and quantitative titres correlated with clinical characteristics.
Structure of MOG
RESULTS:In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2 % of samples high-titer anti-MOG antibodies were identified. In patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r=0.574; p=0.025).
CONCLUSIONS:Thus high-titre reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS.
"MOG is one of the few myelin targets that is available to attack by antibodies. In animals immune responses to this protein can drive relapsing neurological attacks and antibodies can induce demyelination. This study suggests that such antibodies present in MS could contribute to problems. However, that these antibodies are not ubiquitous (common to every one) suggests that autoimmunity to this protein cannot fully account for the problems of MS. However it should be said that other studies have reported a higher incidence of anti-myelin antibodies. It is feasible that different people will react to different myelin proteins, as is known and is likely to occur. However, it may suggest such that antibodies can be produced as a consequence of other damaging entities that could trigger this autoimmunity
Do I think that antibodies that react with targets within the CNS are a problem in MS. Well yes I do and I'm pretty sure of that because we can take antibodies for MSers and inject them into animals and see undesirable effects.