Scientists still looking for MS cause

April 23, 2008

By Jeanne Millsap special to the herald news

Multiple sclerosis is another one of those mysterious diseases of the nervous system. As with many other neurological diseases, scientists haven't yet figured out what causes it, but they are stumbling on promising clues in their research.

Also mysterious to new MS patients is which of them will develop the devastating progressive symptoms that could leave them bedridden, unable to speak or write, or even paralyzed, and which of them might have only the occasional relapse that will leave them still able to live out a relatively normal lifestyle.

According to Dr. Nitin Nadkarni, a Silver Cross neurologist who has a special interest in MS, there is a subset of about 15 percent of MS patients whose disease will run a "relatively benign" course, with relapses running perhaps only every 10 years.

Most MS patients aren't so lucky. Nadkarni said most begin with remitting and relapsing MS, which means they are suddenly struck with symptoms of the disease, then those symptoms gradually fade away. Initially, the symptoms may seem to completely or partially disappear.

But MS patients eventually usually succumb to a downward spiral of disabilities. Many remitting and relapsing patients become chronic-progressive, which means the symptoms don't have a remission -- they just continue getting worse.

This can lead to a significant disability, Nadkarni said, with patients in a wheelchair or bed-bound.

Nerve disease

Multiple sclerosis is a nerve disease that affects the brain and spinal cord. It eats away at the "white matter," or myelin sheaths that wrap around certain brain cells. Myelin sheaths help nerves carry their electrical impulses. With their myelin gone or damaged, the nerves have difficulty carrying those impulses.

The optic nerve might not be able to carry impulses from the eyes, causing blindness. Depending on what myelin sheaths are damaged on which nerves, symptoms can be muscle weakness, trouble with coordination and balance, thinking and memory problems, and sensations such as numbness, prickling, or pins and needles.

Oligodendrocytes are also damaged in MS. They are the cells that make and nurture myelin sheaths. In the beginning of MS, myelin is destroyed, but the oligodendrocytes jump right in and repair the damage to the myelin. That's when the patient goes into remission.

But as the disease progresses, the damage cannot be as easily repaired, and the symptoms may remain rather than go into remission.

Not autoimmune

Nadkarni said he wouldn't classify MS as an autoimmune disease. The immune system is involved, he said, but it might not be a case of immune cells going awry. One theory is that MS is a case of immune cells doing what they do normally, although they are not found where they are usually located.

There is not a hard-and-fast explanation for the cause of MS yet, Nadkarni said, and there are a few theories.

One is that there is a break in the blood-brain barrier that lets immune cells inside the brain where they aren't normally found.

The blood-brain barrier is a tight barrier between the blood and the cells of the brain that keeps many compounds and cells out of the sensitive brain tissue. If there is a break in this barrier that allows activated lymphocytes, which are immune cells, into the brain, a theory suggests that these lymphocytes might begin attacking the brain or, in this case, the myelin and the oligodendrocytes.

This is a relatively new theory, Nadkarni said, one that has been around only the last three or four years.

Other theories

There are other theories on the causes of MS. Some postulate that a virus causes it or a heavy metal or lack of vitamin D in childhood.

There is also some kind of genetic component in MS, because it is more common in those with northern European ancestry.

MS is more common in women than in men, too. Its onset is normally between the years of 20-40, and the severity of the disease seems to be worse the older the onset of symptoms.

Nadkarni said the development of MRI revolutionized the diagnosis of MS. With it, neurologists can see specific areas of "plaques" in the brain, which are lesions where the myelin and oligodendrocytes have been damaged.

There are many treatments for MS, most of which are costly injectables and many of which have some hefty side effects.

The drugs aim to return function after an attack, prevent new attacks, and prevent disability.

There are also a couple of treatments for patients who fail to respond to conventional treatments. One is a monoclonal antibody that binds to lymphocytes to prevent them from entering the brain. Another is a chemotherapy, but that treatment has harsh side effects.

Stem cell therapy is experimental and still in trial, and Nadkarni said he is hopeful of its outcome with MS patients.

With stem cell therapy, patients have some of their young stem cells withdrawn from their blood, then all of the immune cells in their bodies are destroyed with chemotherapy. Those initial stem cells are then injected back in, with the hopes they will migrate to the brain and form new oligodendrocytes.