Unraveling the Mysteries of MS"
By Judy Foreman
06/15/2004

Judi Bartnicki, 53, had been an artist all her life. Then MS, or multiple sclerosis, struck four years ago, doing its worst damage in her left hand, the one she needs for painting and drawing.

"I kept trying to paint and I would drop everything," she said. Finally, her fiance David Richardson, figured out a way to tape her paintbrush to her left hand. Painting is still painful, the Georgetown resident said, "but I am so happy to be able to do it. I am doing my best work."

MS is a nasty, chronic disease in which the immune system attacks the myelin sheath that insulates nerves. It rarely shortens lives, but it does seriously diminish the quality of life of 400,000 Americans, two-thirds of them women. Until recently, doctors had only a sketchy idea of what goes wrong in the brains and spinal cords of people with MS and few drugs to combat it.

But in the last several years, MS "has gone from a mysterious disease with no treatment to a disease we understand, have treatments for, and have a way forward to cure," said Dr. Howard Weiner, head of the Partners MS Center at Brigham and Women's Hospital.

For instance, researchers now think MS may be not one disease but four. They know that even in the early phase when symptoms come and go, the brain is being continuously damaged. They think hormone treatments may help, as may some new medications.

Many, if not most people who get MS have no family history of the disease, although having a parent or an identical twin with MS does raise the risk, said Dr. David Hafler, a professor of neurology at Harvard Medical School.

There appears to be no "MS virus" per se. But doctors believe that some invader, probably a virus, activates so-called TH1 immune cells, which pump out pro-inflammatory chemicals called cytokines. The TH1
cells then mistakenly attack bits of myelin that "look" like the invading virus. The result is severe, patchy inflammation throughout the brain and spinal cord, which cause temporary blindness, muscle weakness, tingling, trouble walking and double vision. TH1 cells also
get into the brain, destroying myelin in brain cells, which causes problems in thinking.

In MS, in other words, the immune system is out of whack, with the pro-inflammatory, TH1 side of the equation overactive, and the anti-inflammatory side -- TH2 and TH3 cells -- underactive.

In recent years, five injectable, prescription drugs have become available to restore this balance, relieve symptoms and slow the disease's progression. Betaseron, Avonex and Rebif directly damp down TH1 cells. Copaxone calms "activated" T cells. Novantrone, reduces the activity of both T and B cells (which make antibodies). A sixth, Antegren, which is still awaiting federal approval, blocks activated TH1 cells from crossing into the brain.

Bartnicki started taking Avonex two months ago and finds it " excellent." "I don't have bad, bad bouts like I used to," she said. "I don't have the terrible muscle spasms I used to have. I can paint for longer periods."

The new understanding of MS is based on several studies, including one by Weiner, who recently published a book, "Curing MS : How Science Is Solving the Mysteries of Multiple Sclerosis. His team used MRIs to regularly scan the brains of 40 MS patients for a year. Even between acute attacks, he found, "the disease is actually progressing."

Dr. Jack Burks, an MS specialist at the University of Nevada School of Medicine in Reno, said "for every attack I see in my office, there are probably 10 attacks that could be seen on an MRI...Now, the big push is to treat early, when patients feel really good."

At the Mayo Clinic in Rochester, MN, Dr. Claudia Lucchinetti, a neurologist, has looked at samples of brain tissue taken from MS patients who were undergoing brain biopsies to exclude other diseases, and at tissue obtained at autopsy from MS patients. She found that the lesions -- damaged spots in the myelin sheath -- are different in different patients, suggesting MS has at least four major subtypes. In one, the damage comes from TH1 cells and macrophages, another type of immune cell. In another, the damage is done by antibodies made by B cells. A third type resembles a viral infection or stroke; the fourth type is characterized by damage in the cells that make myelin. If doctors can find a less invasive way to sort out the types, they might be able to tailor drugs better to each patient.
Hormones also play a role. It's long been known that MS gets better during pregnancy. That's because the fetus consists partly of foreign tissue (from the father), so a woman's immune system must be quieted during pregnancy so that it does not attack the fetus.

In a pilot study, Dr. Rhonda Voskuhl, head of the MS Center at the David Geffen School of Medicine at UCLA, set out to mimic pregnancy by giving estriol, a type of estrogen, to women with MS. She saw a reduction in brain lesions on MRI scans and a favorable shift in the immune balance. When she took the women off the hormone, they got worse.

When she put them back on, they got better again, she said.
Other researchers have been trying, so far with mixed results, to create individualized vaccines to restore immune balance, said Dr. Henry McFarland, chief of the neuroimmunology branch at the National Institute of Neurological Diseases and Stroke, part of the National Institutes of Health.

For symptom relief, injections of Botox, made from the botulinum bacteria, may help relax stiff muscles, allowing some patients to move more easily, said Dr. Michael O'Dell, professor of clinical rehabilitation medicine at Weill Medical College of Cornell University in New York.

The growing understanding of MS clearly provides new hope. But in the meantime, it's important not to "sit around waiting for a miracle," said Dr. Lisa Iezzoni, 49, who has had MS for 27 years and zips around Beth Israel Deaconess Medical Center, where she is a researcher, in a scooter
.
The key, said Iezzoni, who is not taking any MS drugs now, is to "find a doctor who feels comfortable working with you on your terms."

For more information, visit www.nationalmssociety.org.

Judy Foreman’s column appears every other week. Past columns are available on www.myhealthsense.com

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