Multiple sclerosis linked to gene variants
New studies shed light on neurological disease

By Sarah Lindenfeld Hall McClatchy Newspapers

Published on Monday, Jul 30, 2007

RALEIGH, N.C.: Studies published Sunday pinpoint genes that increase the risk of developing multiple sclerosis.

The advances by researchers around the world, including a team at Duke University, are the first major genetic discoveries in more than 30 years that shed light on the neurological disease.

It doesn't mean that people like Michelle Witherspoon, who along with her sister and aunt have multiple sclerosis, will be picking up new medications at the pharmacy next month or even next year. But Dr. John Richert, executive vice president of research and clinical programs for the National Multiple Sclerosis Society, say the discoveries could lead to new drugs in the next five to 10 years.

Witherspoon, of North Raleigh, who works for Cisco Systems, said she's happy with that.

‘‘That's one step closer,‘‘ she said.

The disease is one in which the body's immune system mistakenly attacks the electrical insulation of nerve fibers. The cause is part genetic and part environmental, but researchers trying to identify the relevant genes have endured repeated frustration. Their approach has been to guess what genes might be involved and see if patients have abnormal versions.

This guesswork has produced more than 100 candidate genes in recent years, none of which could be confirmed except for long-known variants in the mechanism used by immune system to recognize proteins that are foreign to the body.

In the three articles published online on Sunday in The New England Journal of Medicine and Nature Genetics, three teams of researchers say they have identified, by separate routes, new genetic variants that contribute to the disease.

One team used a new, advanced gene-hunting method called Whole Genome Association, which has racked up a string of successes with major diseases in the last few months. The other teams used the candidate gene approach, but because all three teams identified the same gene, the researchers say they are confident they have opened a new window into the cause and possible treatment of multiple sclerosis.

First symptoms

Witherspoon was 33 when she first noticed her symptoms.

She lost most of her sight and had a hard time walking and talking. Her sister was diagnosed with the disease years before.

Witherspoon has regained her sight, speech and ability to walk, though symptoms can recur.

‘‘I'm really blessed,‘‘ said Witherspoon, who runs a support group for African-Americans with the disease and is active in a group for working women. ‘‘My impacts are invisible. It's a lot of muscle pain sometimes. I just don't usually talk about it. What can people do?‘‘

Witherspoon takes a shot every other day, which helps slow the effects. She's hopeful a new drug would mean no more needle pricks.

Pieces of puzzle

‘‘It's putting the pieces of the jigsaw together,‘‘ said Simon Gregory, molecular geneticist at Duke's Center for Human Genetics and first author of the paper that appeared in Nature Genetics. ‘‘It's trying to break down what it is that's causing the disease.‘‘

Richert of the MS Society said every new gene that is associated with multiple sclerosis becomes a potential new target for drug development.

‘‘We've got some good drugs available, but they're not fully effective,‘‘ Richert said in an interview. ‘‘They're only partially effective. They do a good job. They alter the course of the disease, but we need to do better.‘‘

The research could prompt new interest in developing Roche Holding AG's Zenapax, a drug that blocks the action of one of the genes, said researchers, including David Hafler, a Harvard Medical School neurologist at Brigham and Women's Hospital in Boston.

About 400,000 Americans have multiple sclerosis. Most are diagnosed between ages 20 and 50.

The gene scientists tracked makes a substance called the interleukin-7 receptor, a protein that enables cells of the immune system to respond to a control agent. Researchers believe the receptor is part of a biochemical pathway involving many genes; defects in any of these genes may lead to the disease. It is now possible to explore the pathway, they say, in the hope of devising treatments to correct the disease-causing process.

Scientists at the U.S. National Institutes of Health are testing Roche's Zenapax, which blocks the interleukin-7 receptor, in multiple sclerosis, Harvard's Hafler said.

‘‘This should fuel the fire for pushing the drug along into further studies,‘‘ he said.

‘‘This is a very good beginning,‘‘ said Kari Stefansson, chief executive of Decode Genetics, a company in Reykjavik, Iceland, that has spearheaded the hunt for genetic causes of common diseases.

‘‘But once you have an ironclad discovery, as I believe the interleukin-7 receptor is, then you have the motivation to endure the expense of a long clinical trial,‘‘ Stefansson said.


--------------------------------------------------------------------------------
The New York Times and Bloomberg News contributed to this artricle.


RALEIGH, N.C.: Studies published Sunday pinpoint genes that increase the risk of developing multiple sclerosis.

The advances by researchers around the world, including a team at Duke University, are the first major genetic discoveries in more than 30 years that shed light on the neurological disease.

It doesn't mean that people like Michelle Witherspoon, who along with her sister and aunt have multiple sclerosis, will be picking up new medications at the pharmacy next month or even next year. But Dr. John Richert, executive vice president of research and clinical programs for the National Multiple Sclerosis Society, say the discoveries could lead to new drugs in the next five to 10 years.

Witherspoon, of North Raleigh, who works for Cisco Systems, said she's happy with that.

‘‘That's one step closer,‘‘ she said.

The disease is one in which the body's immune system mistakenly attacks the electrical insulation of nerve fibers. The cause is part genetic and part environmental, but researchers trying to identify the relevant genes have endured repeated frustration. Their approach has been to guess what genes might be involved and see if patients have abnormal versions.

This guesswork has produced more than 100 candidate genes in recent years, none of which could be confirmed except for long-known variants in the mechanism used by immune system to recognize proteins that are foreign to the body.

In the three articles published online on Sunday in The New England Journal of Medicine and Nature Genetics, three teams of researchers say they have identified, by separate routes, new genetic variants that contribute to the disease.

One team used a new, advanced gene-hunting method called Whole Genome Association, which has racked up a string of successes with major diseases in the last few months. The other teams used the candidate gene approach, but because all three teams identified the same gene, the researchers say they are confident they have opened a new window into the cause and possible treatment of multiple sclerosis.

First symptoms

Witherspoon was 33 when she first noticed her symptoms.

She lost most of her sight and had a hard time walking and talking. Her sister was diagnosed with the disease years before.

Witherspoon has regained her sight, speech and ability to walk, though symptoms can recur.

‘‘I'm really blessed,‘‘ said Witherspoon, who runs a support group for African-Americans with the disease and is active in a group for working women. ‘‘My impacts are invisible. It's a lot of muscle pain sometimes. I just don't usually talk about it. What can people do?‘‘

Witherspoon takes a shot every other day, which helps slow the effects. She's hopeful a new drug would mean no more needle pricks.

Pieces of puzzle

‘‘It's putting the pieces of the jigsaw together,‘‘ said Simon Gregory, molecular geneticist at Duke's Center for Human Genetics and first author of the paper that appeared in Nature Genetics. ‘‘It's trying to break down what it is that's causing the disease.‘‘

Richert of the MS Society said every new gene that is associated with multiple sclerosis becomes a potential new target for drug development.

‘‘We've got some good drugs available, but they're not fully effective,‘‘ Richert said in an interview. ‘‘They're only partially effective. They do a good job. They alter the course of the disease, but we need to do better.‘‘

The research could prompt new interest in developing Roche Holding AG's Zenapax, a drug that blocks the action of one of the genes, said researchers, including David Hafler, a Harvard Medical School neurologist at Brigham and Women's Hospital in Boston.

About 400,000 Americans have multiple sclerosis. Most are diagnosed between ages 20 and 50.

The gene scientists tracked makes a substance called the interleukin-7 receptor, a protein that enables cells of the immune system to respond to a control agent. Researchers believe the receptor is part of a biochemical pathway involving many genes; defects in any of these genes may lead to the disease. It is now possible to explore the pathway, they say, in the hope of devising treatments to correct the disease-causing process.

Scientists at the U.S. National Institutes of Health are testing Roche's Zenapax, which blocks the interleukin-7 receptor, in multiple sclerosis, Harvard's Hafler said.

‘‘This should fuel the fire for pushing the drug along into further studies,‘‘ he said.

‘‘This is a very good beginning,‘‘ said Kari Stefansson, chief executive of Decode Genetics, a company in Reykjavik, Iceland, that has spearheaded the hunt for genetic causes of common diseases.

‘‘But once you have an ironclad discovery, as I believe the interleukin-7 receptor is, then you have the motivation to endure the expense of a long clinical trial,‘‘ Stefansson said.


http://www.ohio.com/lifestyle/health/8802547.html
--------------------------------------------------------------------------------
The New York Times and Bloomberg News contributed to this artricle.