How to reduce the damage when immune systems turn nasty
A DRUG designed thirty years ago to treat multiple sclerosis might suppress a whole range of autoimmune diseases. It produces a shift in the immune system that counteracts the way the body turns on itself, say researchers in the US.
The body can mount two distinct types of immune response: Th1 or Th2. The two are antagonistic--signals that stimulate one inhibit the other and vice versa. In multiple sclerosis, an inflammatory, Th1-type response destroys proteins in the myelin sheath that covers nerves.
In 1967, researchers in Israel synthesised a drug made from amino acids found in myelin basic protein. The drug, glatiramer acetate (GA), seemed to protect the nerves of animals with MS-like diseases, presumably by attracting immune system cells that would otherwise attack myelin. Patients given the drug also had fewer relapses.
But now David Hafler at Harvard Medical School and his team have evidence that the drug alters the immune system in a more general way. They analysed T-cell lines from MS patients before and after a long course of GA treatment, and then looked at how these cells responded to antigens such as myelin basic protein, GA itself, and other proteins and peptides associated with autoimmune disease.
After treatment with GA, T cells are more likely to cross-react with many different peptides. Crucially, they also released Th2 cytokines: signals that should elicit a Th2 response and counteract the Th1 response to the peptides involved in MS.
"It was previously thought it worked by looking like the myelin protein," Hafler says. But it "kind of looks like everything", because it is a random arrangement of four amino acids created before scientists knew precisely how to generate a desired protein. Because GA stimulates a shift away from the damaging Th1 response, Hafler believes that it could be useful for treating autoimmune diseases caused by other antigens. Hafler points out that Igal Gery at the National Institutes of Health near Washington DC recently found that the drug protects mice against an autoimmune eye disease called uveoretinitis.
Roland Martin, of the National Institute of Neurological Disorders and Stroke near Washington DC, has completed a similar but unpublished study of how GA affects T cells. He says that it would be difficult to prove that the shift to Th2 is truly the mechanism behind GA's effectiveness against multiple sclerosis. But he agrees that the theory makes sense.
Source: The Journal of Clinical Investigation (vol 105, p 967)
From New Scientist magazine, 15 April 2000.