Doubt has been cast on the causes of multiple sclerosis
March 05, 2003
By Jerome Burne
Is it time for a rethink of the way we treat the 80,000 people in this country who have multiple sclerosis? Not only did two reviews last month conclude that the main drug used is of limited value, but research just published suggests that the widely accepted theory about the origins of MS may be incorrect.
Multiple sclerosis (MS) is invariably described as an “autoimmune disease” — that is, the immune system turns from defender to attacker and starts destroying the myelin sheath, which is vital for insulating nerves in the brain. Consequently most treatments involve powerful immune-suppressing drugs.
In a highly controversial attack on the conventional approach to MS, published last November in the Journal of the Royal College of Physicians of Edinburgh, Professor Peter Behan, a neurologist at Glasgow University, claimed that the effectiveness of the most widely prescribed drug — beta interferon — was no better than a placebo. Last month two separate studies, one published in the BMJ and the other in The Lancet, raised questions about the effectiveness of beta interferon. While noting a modest effect in reducing the number of relapses, the reports concluded that there was no reliable data for its effect beyond a year, which is quite a problem for a drug treating a lifelong disease.
Dr Abhijit Chaudhuri, a lecturer in neuroscience at Glasgow and a co-author with Professor Behan, explains why none of his MS patients is on beta interferon. “You have to have an injection every other day and the evidence shows that it reduces the number of relapses a patient will have by about a third. Now, since the average patient has one relapse a year, that means that you have to inject a drug, whose side-effects can be quite unpleasant, every other day for three years just to prevent one relapse.
“Even so, if that stopped your decline it might well be worth it. But it doesn’t.”
According to the MS Society, beta interferon is an “important” therapy. “Anything that can be done to reduce the sometimes devastating effects of relapses is useful in treating this disease,” it says.
Behind this debate over drug effectiveness is an increasingly bitter argument about the origins of multiple sclerosis. It is a debate that has enormous implications, not only for the sort of research that should be done and how patients should be treated, but also for an ongoing legal argument involving millions of dollars about whether MS can be brought on by certain sorts of physical trauma, most significantly whiplash in a car crash. Under the autoimmune model such a link makes no sense, whereas if other causal factors are involved the trauma theory gains credence.
Professor Behan, who has testified in the courts to the possibility that trauma triggers a predisposition, outlined a range of criticisms of autoimmune theory in his paper. One involves the animal model used by researchers to study the disease. The model is created by injecting vaccine-like substances into the brains of mice, which cause them to have an autoimmune reaction that damages their myelin sheath.
Professor Behan’s critique concentrates on the many ways in which this induced disorder is quite different from human MS. The significance is that treatments that help these modified mice regularly prove ineffective in humans.
These points were challenged by Alastair Compston, a professor of neurology at Cambridge University, speaking on behalf of the Multiple Sclerosis Society. The animal model, he asserts, is useful if properly used, while “the process of inflammation drives the tissue damage that correlates with MS”.
But Professor Behan is not alone in his thinking. As well as the recent reviews of beta interferon, a paper due out later this month from Dr Massimo Filippi, of the Istituto Scientifico Universitario Ospedale San Raffaele in Milan, casts doubt on one of the basic assumptions of the autoimmune theory. Dr Filippi scanned the brains of patients with early symptoms of MS and found not only signs of extensive damage to neurones, but also that this was “largely independent of what inflammation can be detected”.
In other words, damage doesn’t develop gradually driven by autoimmune inflammation, but is both there at the beginning and not obviously linked with inflammation.
Which brings us to the key question: why do people get MS, if not because of a rogue immune system? We still do not know, but Professor Behan, Dr Filippi and others believe that it is worth looking elsewhere, possibly at metabolic change leading to neurodegeneration, which then might be slowed down or halted.
Support comes from Professor Charles Poser, of Harvard Medical School, one of the grand old men of MS research. “There is undoubtedly a change in immune function with MS but we don’t know if it is a cause or an effect,” he says. “I agree entirely that, given the lack of progress with the autoimmune theory, it would be useful to explore other avenues.”
Jerome Burne is the editor of Medicine Today
Copyright © 2003 Times Newspapers Ltd