Author: Gavin Giovannoni

A new study looking into the immune response to EBV in people with MS has shown that a group of white blood cells responsible for killing EBV, the so called CD8+ cytotoxic lymphocytes or CTLs, are increased in theblood of people with early MS as compared to controls and other patients. Importantly these cells were shown to be increased in the spinal fluid of subjects with MS compared to subjects with other diseases. This data further strengthens the association between EBV and MS, in particular early disease.

Jaquiéry E, et al. Intrathecal immune responses to EBV in early MS. Eur J Immunol. 2009 Dec 16;40(3):878-887. [Click here]

“Gross National Happiness (GNH)” vs. “Gross Domestic Product (GDP)”

Please see Nature Editorial, “Progressive Thinking”.

What do you think?

http://news.bbc.co.uk/1/hi/health/8374980.stm

We remain sceptical about this theory; venous outflow obstruction does not explain the epidemiology of MS and falls down short on many other observations.

The interventions required to relieve venous obstruction are not without risks. The ‘blood blockage theory’ remains a theory and any involvement with the theory should be via ethically approved research studies.

Is direct-to-patient on-line advertising ethical or not? Please see following news piece for a debate on the issue:

Meredith Wadman. Drug ads move online, creating a web of regulatory challenges. Nat Med 2010;16:22. or http://www.nature.com/nm/journal/v16/n1/full/nm0110-22.html

Biogen-Idec and Elan have announced the eminent start of a clinical trial, called Surpass, to assess the effectiveness of switching to natalizumab (Tysabri) in patients that have experienced disease breakthrough with either glatiramer acetate or interferon beta.

I interpret this as a show of confidence by the companies that we can overcome the PML problem; there are now 31 confirmed cases of post-marketing PML in patients with MS receiving natalizumab.

We need your help. Please copy and past this link into your browser’s address field to participate in a survey on end of life issues in relation to multiple sclerosis:

https://www.surveymonkey.com/s/end-of-life-ms-survey

Please send this link to as many people with multiple sclerosis that you know.

Thank you

After our MS Research Day on the 30th January we have been asked by several people about the correct dose of vitamin D to take to try and prevent MS and related disorders. Unfortunately we don’t know. Until we do the appropriate clinical trials any recommendations will not be evidence-based. At present we defer to the Vitamin D Council’s recommendations (www.vitamindcouncil.org):

“…. if you have little UVB exposure, my advice is as follows: healthy children under the age of 1 years should take 1,000 IU per day—over the age of 1, 1,000 IU per every 25 pounds of body weight per day. Well adults and adolescents should take 5,000 IU per day…..”

Before starting vD supplementation at this level we would urge you to see your doctor to discuss things formally; ideally this should be done in conjunction with blood monitoring.

I received a strongly worded email criticising our site for participating in placebo-controlled MS clinical trials; in the opinion of the critic as there are licensed disease-modifying therapies for people with MS, placebo-controlled trials are unethical.

What do you think?

I responded as follows:

“Yes, there are several ethical considerations that need to be taken into account in relation to placebo-controlled MS trials; this issue has been extensively debated and discussed in the literature and there are International guidelines on the conduct of placebo-controlled trials.

In the UK, ethics committees make us insert a statement in the patient information sheet stating that there are licensed therapies and that by participating in a particular study people with MS could be denying themselves active treatment. In addition, we have to reconsent study participants after each relapse and/or confirmed disease progression. In addition, contemporary placebo-controlled trials have rescue arms, which allow study subjects active treatment within a study if their disease becomes active.

It is important to recognise that despite there being licensed therapies some patients don’t want to go onto them because they are injectables; if we did all trials with an active comparator, i.e. an injectable, we would exclude these patients from participating. People with needle phobia and those that have failed injectables because of side effects make up the majority of patients volunteering for placebo-controlled trials. I suspect, however, that once oral therapies are licensed for MS it will become very difficult to recruit subjects for placebo-controlled trials.

The issue of placebo-controlled trials should also be viewed on the background of the limited efficacy of the current injectables and the fact that we still don’t have data on whether or not they impact on the long-term prognosis of the disease.

In summary, I don’t think it is unethical to do placebo-controlled trials. However, you have to do them with carefully designed trials and informed consent. People with MS are perfectly capable of making an informed decision about not taking up the option of going on to a moderately effective first-line therapy and volunteering for a placebo-controlled trial of a new agent. At the end of the day we need to be pragmatic; without clinical trials we won’t advance the field and people living with MS are very aware of this. “

Please have your say if you agree or disagree with this stance!

On the 22nd January the FDA approved dalfampridine (Ampyra, Elan/Acorda Therapeutics) extended-release tablets to improve walking in people with MS. Dalfampridine is a potassium channel blocker, that has been shown to improve walking speeds vs placebo. The drug was previously known as fampridine sustained release. Given at doses greater than the recommended 10 mg twice a day, dalfampridine can cause seizures. The most common adverse events reported in clinical trials were urinary tract infection, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhoea, indigestion, throat pain, and burning, tingling, or itching of skin. Dalfampridine, should not be used in patients with moderate or severe kidney disease. In these patients, blood levels with the drug approach those associated with the occurrence of seizures.

Please see previous posting below discussing the concerns with dalfampridine.

A NEW STUDY ON INITIAL EBV INFECTION AND MS

Ascherio et al. Primary EBV infection and MS. Ann Neurol 2010; in press.

“In this study all EBV-negative subjects (10 out of 10) who developed MS became EBV positive before MS onset. In contrast, only 36% (10 of the 28) controls subjects who were EBV-negative became EBV-positive with follow-up. Ascherio and colleagues conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection.”

Interpretation: This study is very important with regard to pinning down whether or not EBV causes MS. It ticks one of the criteria for causation; i.e. the correct temporal sequence. You need to get infected with EBV prior to MS onset.

Prof G