NHS Evidence Health Information Resources formerly National Library for Health

The first trial of a DNA-based vaccine for multiple sclerosis has shown promising results, reported three newspapers (14 August 2007). The longer reports were generally accurate. This was a preliminary trial and more research is needed to evaluate the effectiveness of the vaccine.

Three newspapers (1-3) reported on 14 August 2007 that a DNA-based vaccine may reduce damage to the nervous system in patients with multiple sclerosis (MS).
The reports were based on a small randomised controlled trial published in Archives of Neurology (4). Thirty people with MS received the DNA-based vaccine or a placebo. The vaccine was safe and well tolerated. Participants treated with the vaccine showed a decrease in activity of immune cells and antibodies that damage the nervous system in people with MS. Lesions in the brain detected by magnetic resonance imaging (MRI) tended to decrease in number and volume in the vaccine-treated group but increased in the placebo group.
This was a well-conducted preliminary trial. The reports in The Daily Telegraph (1) and The Guardian (2) were generally accurate, and both noted that a larger trial of the vaccine is now underway. The Guardian stated that all the patients in the study had the relapsing-remitting form of MS when in fact patients with secondary progressive MS were also included. The report in The Sun (3) was brief and did not mention the preliminary nature of the research.

Evaluation of the evidence base for DNA-based vaccine treatment for multiple sclerosis

Where does the evidence come from?

The evidence comes from a study by Dr Amit Bar-Or and colleagues at four academic institutions in the USA and Canada. The study was funded by Bayhill Therapeutics, Inc., the company that developed the vaccine.

What were the authors' objectives?

To assess the safety and effects on immune response of BHT-3009, a DNA-based vaccine encoding human myelin basic protein, in patients with MS.

What was the nature of the evidence?

This was a randomised controlled trial involving 30 people with MS. Of the included participants, eleven had relapsing-remitting MS, 13 had secondary progressive MS without relapses and six had secondary progressive MS with relapses. Participants were not taking other disease-modifying drugs and had either lesions detected by brain MRI, a relapse in the previous two years or disease worsening in the previous two years.

What interventions were examined in the research?

Participants were randomly assigned to receive intramuscular injections of BHT-3009 or placebo at 1, 3, 5 and 9 weeks after randomisation. Three different doses of BHT-3009 were tested and BHT-3009 was given with or without atorvastatin. Participants initially randomised to placebo crossed over to receive BHT-3009 from week 13 onwards. Participants were followed for 50 weeks from the start of the study.

What were the findings?

Adverse events related to treatment with BHT-3009 were brief and mild to moderate in severity. The percentage of participants with adverse events was no greater in the BHT-3009 group than in the placebo group. Eight clinical relapses were reported during the trial but only one of these occurred while taking BHT-3009. There was a trend towards a reduction in number and volume of MRI-detected brain lesions in the treatment group compared with the placebo group. There was a decrease in proliferation of myelin-reactive T cells in the peripheral blood and a reduction in myelin-specific autoantibodies in the cerebrospinal fluid in participants treated with BHT-3009 compared with baseline values. Treatment with BHT-3009 + atorvastatin did not produce substantial benefits compared with BHT-3009 alone.

What were the authors' conclusions?

BHT-3009 is safe and induces antigen-specific down-regulation of autoimmune activity with an associated reduction of inflammatory lesions detected by brain MRI.

How reliable are the conclusions?

This was a generally well-conducted randomised trial. Randomisation was performed by an independent organisation and the main part of the trial was performed under double-blind conditions (participants and investigators unaware of treatment allocation). While the results appear promising, the trial represents an early stage in the evaluation of BHT-3009. The number of participants involved was small and the trial was mainly designed to assess safety. The data on other outcomes were derived from even smaller numbers of participants and much more research will be needed to see whether effects on the immune system translate into clinical benefits. A larger placebo-controlled trial of BHT-3009 is now in progress.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

There were no related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR) or on the Database of Abstracts of Reviews of Effects (DARE).