Thursday, June 14, 2007

Breakthrough in multiple sclerosis research

Scientists detect protein that may be key to the disease

Kavita Mishra, Chronicle Staff Writer
Thursday, June 14, 2007

Stanford researchers reported new findings Wednesday that they say bring them closer to understanding what causes multiple sclerosis.

In the report published in the online version of the journal Nature, the researchers implicated a protein that they believe normally regulates the human immune system, but doesn't do so in people with the lifelong illness.

The researchers, led by Stanford neurologist Lawrence Steinman, said they are optimistic their discovery will lead to new treatments for patients and possibly a way to stop the disease's progression.

For Joyce Bruno, one of the 400,000 people in United States with multiple sclerosis, the report was good news.

"Even if it isn't the answer for me, I have a feeling it's going to be an answer for someone," the Walnut Creek resident said.
In 1990, Bruno started to drag her left leg and felt intense muscle cramps in both legs. An MRI of her brain revealed she had signs of multiple sclerosis, and her doctor told her the haunting word "incurable."

She was forced to retire from managing funds at a mortgage company four years later, at the age of 44, and now uses a cane to walk.

Most people with multiple sclerosis experience a range of symptoms -- from daily fatigue and weakness to blindness and paralysis. They are diagnosed early in adulthood and experience symptoms, as the immune system attacks nerve cells, intermittently throughout life. To avoid a whirlwind progression of these symptoms, they take steroids and other drugs to suppress the immune system and control the disease.

Siblings and close relatives have a higher risk of the disease. Doctors currently tell patients that the disease is caused by a mixture of bad genes and environmental factors. But the work by Steinman and his team is putting new focus on a protein in the body called alphaB-crystallin.

The researchers found that people with multiple sclerosis had more alphaB-crystallin in their bodies than people without the disease. They looked at the protein, usually found in high levels in the lens of the eye and in muscle, in both humans and mice.

In mice that were designed to lack the protein and had a multiple sclerosis-type illness, the disease worsened. When the protein was given back to the diseased mice, the illness improved, showing that the protein could help check the hallmark inflammation of the disease.

But scientists then looked at the fluid in multiple sclerosis patients that cushions the brain and spinal cord, where the disease manifests. There, they found more protein and surprisingly more antibodies to the protein, said lead author and Stanford neuroscientist Shalina Ousman. The antibodies, they concluded, prevent the protein from working properly, causing more inflammation.

The researchers don't know yet if giving more protein to a multiple sclerosis patient would overwhelm the antibodies to fight the disease or if getting rid of these antibodies would help patients, she said.

Steinman said he believed people with multiple sclerosis developed antibodies to the protein like an allergic reaction to a bee sting. Giving people small amounts of the protein when they didn't have symptoms could sensitize the body to make less antibodies. That would free up the protein to quell the immune system when there is inflammation with the disease.

Dr. Douglas Goodin, director of the UCSF Multiple Sclerosis Center, who was not involved in the study, said he could see how a drug could be made from the protein but wanted more research into how it contributed to the disease before recommending it to patients.

Multiple sclerosis gained some attention in recent years on the TV show "The West Wing" when Martin Sheen's character, the president, survived impeachment over charges that he hid his disease.

People who live close to the equator tend not to develop it. Scientists think those who get more sun at a younger age have more vitamin D in their bodies, which may keep them from developing the disease. Despite these promising correlations, several common viruses, like Epstein Barr, which causes mononucleosis, have also been linked to multiple sclerosis, Goodin said.

E-mail Kavita Mishra at