JOSEPH BATTAGLIA, MD: A defining feature of schizophrenia is that there is a deterioration in functioning for a minimum of about six months or so. But people often go for a long period of time without getting treatment while they're having symptoms even though they know something is going on. They're trying to understand it and sometimes they gravitate towards drugs or alcohol to try to self-medicate, but they're very ashamed, they're very frightened of what's taking place.

What do you do if you think a family member has it?
JOSEPH BATTAGLIA, MD: Schizophrenia doesn't go on 24 hours a day, it ebbs and flows with the voices and delusions. In this case, you don't "strike when the iron's hot" -- you have to approach it when the iron's cold. Wait until the emotions die down, which means the positive symptoms, until they're not active. That's how you approach someone to reduce the risk that they're going to show some aggression.

What is the treatment for schizophrenia?
JOSEPH BATTAGLIA, MD: There have been some recent developments, but prior to the last 10 years, the mainstay was medications that blocked dopamine. What they would do was reduce hallucinations and delusions. But they didn't improve someone's cognitive abilities or improve their emotional feelings. There was a realization that just reducing hallucinations and delusions didn't guarantee someone was going to get better.

Now there's evidence to show that cognitive therapies are very helpful, vocational, reintegration with work, family therapies -- that the three combined actually give someone the best chance of continuing to do well.

Can people with early schizophrenia manage the condition themselves?
ANTHONY SALERNO, PH.D.: Learning the symptom management skills and stress management skills are extremely important. It would be nice, if medication was the cure-all, but it's not. An individual needs to put considerable effort and energy into managing their symptoms, and there are techniques and skills to cope more effectively, and that's a very important part of what practitioners need to do.

JOSEPH BATTAGLIA, MD: Progress is really hard to make on the short-term basis. The issue about outcome is that within 25 or 30 years, 50% to 60% do not return to normal, but can be functioning with part-time jobs and an increased social network.

New MS Drugs Wait in Limbo

  A year after it was pulled for safety concerns, a promising treatment for multiple sclerosis seems poised to return. The drug, Tysabri, was pulled off the market last February, after two patients developed a rare brain disorder, known as progressive multifocal leukoencephalopathy, or PML. A third case was later found in a trial that was testing the drug for Crohn’s disease, another immune disorder.

Two of the patients eventually died from complications. But an internal review by the company that makes Tysabri found no further PML cases in any of the patients who used the drug in clinical trials. On March 7, an advisory committee for the Food and Drug Administration will mull over the risks and make recommendations about whether Tysabri should be reinstated.

Experts are hopeful. Tysabri, which was approved by the FDA in the fall of 2004, is a potent treatment, reducing disease flare ups by more than half when added to one of the leading multiple sclerosis drugs, Avonex. The FDA recently allowed clinical trials on Tysabri to resume.

Yet, concerns remain. How can doctors make sure these rare side effects don’t show up again, especially if more and more patients start to take Tysabri? And equally important, what do these troubles mean for similar treatments that are meant to usher in a new age of fighting multiple sclerosis?

We have to get this right." says Dr. Elliot Frohman of the University of Texas Southwestern Medical Center, whose patient is the lone survivor of PML side effects from the drug. "If we don’t solve the problems for Tysabri, everything else is dead in the water."

New Drugs, New Concerns?
The source of the trouble stems from the way newer drugs like Tysabri target the disease. Multiple sclerosis is caused by an immune system malfunction, leading to inflammation, which can ultimately destroy the protective substance that blankets nerve fibers.

Rather than just clamping down on inflammation all together, Tysabri goes after a select group of errant immune cells. However, these cells also offer some protection against viruses and other infections, which means that even the most targeted approach might cause unforeseen side-effects.

Newer drugs that follow in Tsyabri’s footsteps target different abnormalities. But these, too, have the potential to push the immune system past its defensive tipping point.

"All these drugs have the same inherent problem." says Frohman, who has studied many of them.

Still, as Tysabri shows, the benefits are appealing. "This is the best treatment we’ve seen." he says.

As a precaution, Frohman recommends that doctors take blood tests of those who are taking Tysabri, should the drug be let back on the market. Virtually everyone carries the virus that causes PML. If the amount of virus in the blood shoots up, then treatment might be stopped in time before the drug can cause any harm.

"We can’t let our guard down." says Frohman.

Stakes are High
Indeed, Tysabri is the first real test case in a range of new strategies that are being studied for multiple sclerosis. The mainstay therapy has long been drugs called interferons, which have shown modest effects. Newer treatments like Copaxane are approved for multiple sclerosis that relapses, but these are not having as big an impact on the disease as hoped.

"We are always in need of better treatments." says Dr. Patricia O’Looney, the director of biomedical research at the National Multiple Sclerosis Society.

In the meantime, doctors rely on a grab-bag of different drugs that, while not specifically approved for treating multiple sclerosis, do show some help in controlling symptoms.

"We do it all the time." Frohman says of using drugs off-label, which is common in some other diseases as well.

The most popular are steroids and non-specific immunosuppressant drugs, such as azathioprine. But this could eventually change. At least 140 clinical trials are now underway for multiple sclerosis, with several new drugs approaching late-stage testing.

Some of the most promising include treatments that are already approved for a different disease, such as cholesterol-lowering statins, the cancer treatment Rituximab and drugs that are used to suppress the immune system after a transplant. Tysabri, which is closest to being approved, needs to be injected. But a pill version of newer multiple sclerosis treatments are also being studied.

"The good news." Dr. O’Looney says, "is that there is so much in the pipeline that approaches the disease from so many different angles."

Frohman says that his patient who survived PML is a constant reminder for researchers to get it right.

"It’s been humbling." he says.