Genetic find raises hope for Canada's MS patients

ANDRÉ PICARD

From Monday's Globe and Mail

July 30, 2007 at 4:06 AM EDT

Researchers have identified two genetic markers that increase a person's risk of developing multiple sclerosis, a mysterious and unpredictable disease that strikes people, women in particular, in the prime of their lives.

The findings, the first breakthrough in 30 years of genetic research, will have no immediate impact on the estimated 75,000 Canadians who have the disease, with about 1,000 new cases diagnosed each year.

But knowing that there are at least two genes linked to MS - each of which increases risk by about 30 per cent - should allow scientists to pursue their research along three avenues:

The possibility of predicting if a person will develop MS;

The ability to better predict the course of an unpredictable disease; and

The possibility of new treatments.

"Having this genetic road map will be of incredible importance in developing new therapies," said neurologist David Hafler.

The Harvard Medical School professor is lead author of the study, which was published yesterday in the online version of the New England Journal of Medicine.

A second study, led by Simon Gregory, a molecular geneticist at the Center for Human Genetics at Duke University in Durham, N.C., was published simultaneously in Nature Genetics.

Multiple sclerosis is an autoimmune disease caused by a breakdown of myelin, a fatty substance that coats nerve cells and plays a crucial role in transmitting messages in the central nervous system. When those messages are blurred, nerves malfunction, causing all manner of woes, including blurred eyesight, loss of sensation in the limbs and even paralysis.

As best as scientists can determine, MS has a genetic basis, but requires environ- mental triggers. Exposure to a virus in childhood, vitamin D deficiency and sex hormones are believed to play a role.

The disease is found most commonly in people of northern European background and in countries furthest from the equator. About 2.5 million people worldwide suffer from MS, and Canada has one of the highest rates in the world.

"MS is enormously complex and this research confirms that complexity," said Aprile Royal, assistant vice-president of medical information and education at the Multiple Sclerosis Society of Canada.

"It's like a giant jigsaw puzzle and now we have another important part of that puzzle," she said.

The two studies involved scanning DNA samples from more than 20,000 MS patients and unaffected individuals in the United States and Europe, and looking for single nucleotide polymorphisms (SNPs), which are single-letter variations in a gene's DNA code.

Both research studies, using different methods, found an association between MS and a single SNP in the gene interleukin 7 receptor-alpha (IL7R-alpha). One of the studies also found two SNPs in the gene for interleukin 2 receptor-alpha (IL2R-alpha) associated with the disease.

Both receptors are known to influence the way regulatory T cells patrol the body for pathogens. T cells suppress activation of the body's immune system. The genes are on chromosome 5.

Previously, the only genetic link identified with MS was a large cluster of genes essential to the immune system known as the major histocompatibility complex, or MHC, which is found on chromosome 6.

Ms. Royal, a nurse who has worked in the MS field for 25 years, said some people will be discouraged by the fact that the new findings are incremental in nature, and will not result in dramatic changes tomorrow.

"It's easy for people to get discouraged but they have to keep this in context," she said. "The volume and speed of MS research has been incredible.

"What's happening today is like a nuclear explosion of knowledge compared to when I started."