Calming Factor: DNA vaccine for MS passes initial test: Science News Online, Aug. 18, 2007

Nathan Seppa

An experimental vaccine for people who have multiple sclerosis has proved safe, clearing a necessary first hurdle toward regulatory approval. The results of this initial trial also suggest that the vaccine can indeed quell the self-destructive immune reaction that many scientists believe causes the disease.

Despite this early promise, the researchers caution that the findings are based on data gathered from a small group over a limited time.

The researchers used a technique called DNA vaccination, which introduces a gene into the body to elicit an immune response. But rather than rile the immune system against a foreign foe, the new multiple sclerosis (MS) vaccine seeks to induce immune tolerance of myelin basic protein, a component of myelin. A fatty material that protects nerves, myelin is degraded in MS, robbing patients of muscle control.

For the vaccine, researchers at Stanford University and Bayhill Therapeutics in Palo Alto, Calif., designed a DNA ring that encodes a slightly altered version of myelin basic protein. The changes replaced immune-stimulating parts of the protein with immune-suppressing ones.

Scientists gave 30 MS patients four injections over 9 weeks and then tracked their progress for a year. The study was made public this week and will appear in the October Archives of Neurology.

Periodic magnetic resonance imaging of the patients' brains showed that inflammation associated with the nerve damage of MS didn't worsen as a result of the vaccine.

Eight MS flare-ups, or relapses, occurred among the patients during the study, but seven of these struck patients who had finished receiving the vaccine, says study coauthor Amit Bar-Or, a neurologist and immunologist at McGill University in Montreal. These results allayed concerns that the vaccine might exacerbate MS.

Spinal fluid obtained from three patients before and after getting the vaccine showed a reduction in rogue antibodies that react against myelin. In addition, blood samples from five patients showed a decrease in immune T cells that react to myelin.

"This is an important development in the field of MS therapy," says immunologist Gérald J. Prud'homme of the University of Toronto, who wasn't part of the study team. "This is the first demonstration of a beneficial effect of DNA vaccination in a clinical trial of autoimmune disease."

The vaccine may inhibit myelin damage in several ways, Bar-Or says. For example, the vaccine's DNA apparently enters the nuclei of dendritic cells and other traffic cops that orchestrate immune reactions, he says. Because of the DNA's tweaked structure, the myelin basic protein that these cells then produce isn't seen as an enemy, and other immune cells decrease their responses against it.

This calming effect may extend to immune cells targeting central nervous system proteins besides myelin basic protein. However, more work needs to be done to confirm this, Bar-Or says.

Meanwhile, the findings have cleared the way for a larger trial designed to assess whether the therapeutic vaccine can limit the nerve damage that marks MS. In that study, researchers have already given 290 patients a longer course of the vaccine than the safety study entailed. The team expects to release the results of the current study within the next year.

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References:

Bar-Or, A., et al. In press. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled Phase 1/2 trial. Archives of Neurology. Available at http://dx.doi.org/10.1001/archneur.64.10.nct70002.

Further Readings:

Garren, H., et al. 2001. Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway. Immunity 15(July):15-22. Abstract available at http://dx.doi.org/10.1016/S1074-7613(01)00171-6.

Prud'homme, G.J. 2004. Altering immune tolerance therapeutically: The power of negative thinking. Journal of Leukocyte Biology 75(April 1):586-599. Available at http://www.jleukbio.org/cgi/content/full/75/4/586.

Ruiz, P.J., et al. 1999. Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: Modulation of T cell costimulation. Journal of Immunology 162(March 15):3336-3341. Available at http://www.jimmunol.org/cgi/content/full/162/6/3336.

Steinman, L. 2007. A brief history of T_H17, the first major revision in the T_H1/T_H2 hypothesis of T cell-mediated tissue damage. Nature Medicine 13(February):139-145. Abstract available at http://dx.doi.org/10.1038/nm1551.

Sources:

Amit Bar-Or
McGill University
Montreal Neurological Institute
3801 Rue University
Montreal, QC H3A 2B4
Canada

Gérald J. Prud'homme
Department of Laboratory Medicine and Pathobiology
University of Toronto
St. Michael's Hospital
30 Bond Street, Room 2013CC
Toronto, ON M5B 1W8
Canada

From Science News, Vol. 172, No. 7, Aug. 18, 2007, p. 99.

http://www.sciencenews.org/articles/20070818/fob2.asp