Monday, 27 December 2010

Placebo vs. interferon-beta in combination with mycophenolate

24 treatment-naïve RRMS patients participated in a 1 year prospective safety study. There were no differences were identified between the two treatment groups with respect to patient-reported adverse events or laboratory abnormalities. The combination treatment regimen of interferon beta-1a and mycophenolate was well tolerated.

The investigators conclude: "Despite the small sample size, therapeutic trends were observed in favor of combination therapy. An adequately powered controlled trial of mycophenolate in MS appears warranted."

Remington et al. Ther Adv Neurol Disord. 2010 Jan;3(1):3-13.

I couldn't agree more with the investigators; given the current dogma concerning the autoimmune pathogenesis of MS, mycophenolate should be given a chance. The problem is that with the imminent launch of several oral therapies, will it be possible to design an affordable trial to test mycophenolate in RRMS? I suspect not!

Mycophenolate vs. Interferon-beta: an underpowered study

Mycophenolate is an anti-rejection agent widely used in transplantation. This was a randomised, 6-monthly, study to compare the effectiveness of mycophenolate to interferon beta in 35 untreated patients with RRMS. Not surprisingly there was no difference between mycophenolate and interferon beta therapy treatment groups. The mycophenolate group showed a trend toward a lower accumulation of lesions on MRI, but this was not significant. This study was simply too small to draw any conclusions (underpowered). It should have been appropriately powered to give a definitive answer; the worrying consequence of this study is will anybody be brave enough now to do a definitive trial? Has this study killed a potentially promising oral agent?

Frohman et al. Ther Adv Neurol Disord. 2010 Jan;3(1):15-28.

Is it ethical to do under-powered studies? NO!

Should people with MS who volunteer to participate in treatment trials expect the studies to be appropriately powered? YES!

Wednesday, 22 December 2010

If you can; get your walking shoes on!

Walking impairment in patients with multiple sclerosis: exercise training as a treatment option; "exercise training and physical activity might hold significant potential for the management of progressive mobility disability in MS."

Motl et al. Neuropsychiatr Dis Treat. 2010 Nov 16;6:767-74.

Monday, 20 December 2010

At last the published results of the anti-IL12 & anti-IL23 trial

Until recently the cytokines* interleukins 12 and 23 were believed to be very important in driving inflammation in MS. A drug that neutralises these cytokines has failed to have the desired effect on the disease thus questioning the current dogma. As a result of this study most immunologists have changed their thinking about the disease. Although this trial was negative the people with MS who volunteered to participate in this study have made a very valuable contribution to the field. Negative trial results can be as important as positive ones; in this case the results have changed the way we think about the disease.

Vollmer et al. Mult Scler. 2010 Dec 6.

* cytokines is a term immunologists use to describe the protein messages that cell send to each other to communicate; not too dissimilar to the role of hormones!

Statins for MS?

This review confirms our advice that there is insufficient evidence to support statins (cholesterol lowering drugs) as a treatment for MS.

Wang et al. Cochrane Database Syst Rev. 2010 Dec 8;12:CD008386.

A good vitamin D update

THE AUTHORS' CONCLUSIONS ARE SELF-EXPLANATORY: "The current level of evidence for the effectiveness of vitamin D supplementation in the management of people with MS is based on a single randomised control trial with potential high risk of bias, which does not at present allow confident decision-making about the use of Vitamin D in MS. Therefore, until further high quality evidence is available, clinicians may wish to consider relevant MS guidelines on vitamin D supplementation when making decisions about the care of people with multiple sclerosis. Adequately powered, multi-centred RCTs with a focus on clinical as well as immunological and MRI outcomes that are meaningful to people with MS, and are able to provide insight into the benefits of Vitamin D in people with MS, are still required."

Jagannath et al. Cochrane Database Syst Rev. 2010 Dec 8;12:CD008422

New evidence that natalizumab reduces axonal damage

Natalizumab treatment markedly reduces the release of neurofilament into the spinal fluid of people with MS. Neurofilaments are the main structural protein of neurons and axons. This is further evidence that natalizumab treatment reduces the accumulation of nerve injury in MS. Hopefully, this will stimulate pharmaceutical companies to include spinal fluid neurofilament analysis in all of their clinical trials.

Gunnarsson et al. Ann Neurol 2010

Pregnancy and foetal outcomes after interferon-β exposure in multiple sclerosis

A report on 88 pregnancies in Italian woman that were exposed to interferon-beta (average exposure 4 to 5 weeks) has demonstrated that exposure to interferon-beta was not associated with an increased risk of spontaneous abortion. However, it was associated with both a lower baby weight and length. No significant fetal complications, malformations, or developmental abnormalities were noted with a follow-up of 2 years. These findings point to the relative safety of IFNβ foetal exposure of up to 4 weeks during pregnancy. These data will assist woman with MS on interferon beta with difficult decisions with regard to pregnancy.

Amato et al. Neurology 2010;75:1794-802.

Monday, 6 December 2010

Friday, 3 December 2010

How much vitamin D is too much?

If you interested please read the Institute of Medicine's 2010 report on vitamin D and calcium intake.

Click here for on-line access to the report

The committee of scientists, convened by the National Academies' Institute of Medicine, doubled the upper level of vitamin D that people that people between the ages of 9 and 50 can safely take in any given day from 2,000 to 4,000 IU.

Please click here to read a commentary in Science News

Wednesday, 1 December 2010

MS Endophenotype Study


MS is a common, complex neurological disease. Although the precise aetiology of MS is not yet known numerous studies indicate that both genetic and environmental factors are important. It now appears that the environment acts long before MS becomes clinically evident and suggests the existence of a prodromal phase for the disease. The possibility of a prodrome indicates a window of opportunity to potentially reverse early disease processes before clinical disease becomes evident. Studying a prodrome requires techniques other than clinical observation such as monitoring "endophenotypes" that result from associated risk factors. Identifying and studying individuals, for example family members of people with MS, with a high risk of developing the disease provides a powerful opportunity to understand the MS causal cascade and is highly relevant to strategies that are aimed at preventing this debilitating disease.

We are therefore recruiting people with MS who have brothers and/or sisters without MS, and people with MS who are twins (identical and non-identical) to explore the possible cause of MS. Twins will help us understand the cause of disease and the influence of early environmental exposures; identical twins have the same genetic background and twins in general share the same early environment, which can be different when looking at non twins and unrelated individuals.

If you can help please click here for more details