article: advancing on MS: new drugs and hopes for a vaccine

[Guest guest]

Interesting that they are targeting the Epstein-Barr virus in the

cause for MS. My allergist on his release for getting a flu shot

excluded those with E-B virus (from GSK form). How does one test for

the E-B virus? Do ASD kids harbor this? any research on this??

______

Advancing on MS: New drugs and hopes for a vaccine.

By Marie McCullough

Inquirer Staff Writer

Barely 15 years ago, doctors could do nothing to change the course

of multiple sclerosis, the disabling neurological disease that

strikes in the prime of adulthood.

Today, six drugs are approved to decrease the periodic immune

attacks that underlie MS, another six are in final human testing,

and dozens more are in development. Researchers have zeroed in on

genetic and environmental risk factors; a common virus may play a

role in activating the disease. And the ultimate goal - regrowing

damaged nerves - is no longer a pipe dream.

" I think a regeneration process may be available in the next five to

10 years, " said Abdolmohamad Rostami, chair of neurology at

Jefferson University, where researchers have partially reversed

nerve damage in mice. " I'm very optimistic. "

Rostami joined other MS researchers at last month's annual

conference of the National Multiple Sclerosis Society's Greater

Delaware Valley Chapter. It was attended by more than 2,000

patients, health-care providers and advocates.

Without being pollyannaish about the prospects for curing MS, the

experts agreed that huge strides have been made in managing and

slowing the disease.

" We're treating people much earlier, so they're getting more years

of exacerbation-free time, which we believe will reduce the long-

term disability, " said Clyde Markowitz, director of the MS Center at

the Hospital of the University of Pennsylvania.

In MS, infection-fighting white blood cells attack the protective

myelin covering that insulates nerve fibers in the brain, spinal

cord and eyes. Like broken electrical cables, the inflamed myelin -

and, eventually, nerves - become unable to conduct the brain's

signals. This can cause impaired vision, numbness, mental problems,

and paralysis.

About 10 percent of patients become steadily and progressively more

disabled without clear autoimmune attacks. But most of the country's

400,000 patients - 11,000 in this region - experience relapses of

varying severity and frequency, with complete or partial recovery in

between.

Disability accumulates over time, but MS is maddeningly

unpredictable and rarely fatal in itself.

" It's been over two years since I had a flare-up, " said Carol

, 58, of Philadelphia.

Although she rode around last month's conference on a scooter to

conserve her energy, she can still walk, 31 years after diagnosis.

" If I'm in church, I get an escort to help me, " she said. " But I can

get up and go to the bathroom. I'm so thankful I can still do that. "

Circumstantial evidence has long supported the idea that MS is

triggered by an infectious agent, perhaps a virus or bacteria, in

people with genetic susceptibility.

Now, research is bolstering suspicion that Epstein-Barr virus is the

culprit.

Epstein-Barr is a ubiquitious microbe that infects about 95 percent

of American adults. Often there are no symptoms, but more than a

third of infected adolescents and young adults develop the fever,

sore throat and fatigue of infectious mononucleosis.

A history of mono increases the small risk of MS as much as

threefold. Studies suggest Epstein-Barr also plays a role in lupus,

another autoimmune disease.

Last year, Harvard University scientists reported using stored blood

samples to show that 42 MS patients had abnormally high levels of

antibodies against Epstein-Barr. The antibodies spiked 20 years

before the onset of MS symptoms, then stayed high.

Another clue was published last month: Italian researchers found

remnants of Epstein-Barr infection in the autopsied brain tissue of

MS patients.

While the viral link is controversial, it is raising hopes that MS

could be prevented with a vaccine, just like measles or polio.

" Collectively, the results . . . provide compelling evidence, " said

Alberto Ascherio, senior author of the Harvard study. " I think this

new data on MS will generate new interest in developing a vaccine "

against Epstein-Barr, he added.

Meanwhile, scientists are learning more and more about the immune

system's role in MS.

The six MS drugs approved since 1993 target various molecules that

enable infection-fighting blood cells - T cells and B cells - to

communicate and mobilize. The challenge has been finding a way to

suppress the immune system that is powerful enough to be effective

in most MS patients - yet not so powerful that it leaves them

vulnerable to other diseases.

Tysabri, approved in 2004, turned out to be so good at clamping down

on immune cells that a few patients developed a rare, overwhelming

viral infection of the brain; the drug now carries a warning.

Fingolimod, an experimental drug now in final human testing, is also

designed to rein in immune cells, but earlier in the mobilization

process. It keeps them from leaving the lymph nodes where they're

produced.

" We're getting close to being able to control the destructive immune

process, " said Richert, vice president of research at the

National Multiple Sclerosis Society. " It may come at the price of

side effects that are devastating. But we hope we can find a risk-

benefit balance. "

Whether reducing relapses will ultimately lessen patients'

cumulative disability is not yet clear. But that's the hope,

especially as scientists discover new molecules to manipulate.

At Jefferson, neuro-immunologist Fitzgerald has shown that

interleukin 27, an immune system signaling hormone isolated five

years ago, can suppress an MS-like disease in mice, apparently by

turning other interleukin molecules on or off.

Fitzgerald, 28, has a personal reason to be passionate about her

work: Seven years ago, a mysterious bout of spinal cord

inflammation, perhaps triggered by an undetectable infection, turned

her from an athletic doctoral student into a paraplegic - in a

matter of hours.

" I was in the hospital for five weeks, on steroids. From there, I

made an excellent recovery, " she said. " But knowing what paralysis

feels like, and how hard the recovery period is, and the exhaustion -

it gives me the commitment to this research. "

Commitment is crucial. Thirty years ago, a gene variant was linked

to MS in about half of patients. The next major genetic advance

didn't come until four months ago, when an international research

team identified variants of two more genes that significantly raise

the risk of MS.

" Genetic studies will eventually lead us to the cause of MS and make

it easier to prevent, " Richert said. " But in the short term, each of

these genes offer a new therapeutic target. "

Along with novel therapies, existing drugs may become part of the

treatment arsenal. Among those showing promise: Daclizumab, now used

to prevent kidney transplant rejection; Rituximab, approved to treat

non-Hodgkin's lymphoma and the autoimmune (rheumatoid) form of

arthritis; popular antidepressants known as SSRIs; and an anemia

therapy called Erythropoietin.

There are clues that " natural " substances may work against MS as

well. Estriol, a form of estrogen being given to women with MS in a

trial led by the University of California at Los Angeles, is

normally produced only during pregnancy - a time when MS often goes

into remission. Vitamin D, easily derived from sun exposure, may

help explain why MS is rare in equatorial countries while

comparatively common in sun-deprived places such as Scandinavia.

At Jefferson, both glucosamine, the dietary supplement for joints,

and a compound derived from ordinary soy have been shown to partly

restore walking ability in mice with an MS-like disease.

One of the biggest obstacles to the search for new treatments has

been measuring their impact in humans. That obstacle is crumbling,

thanks to research led by the University of Pennsylvania and s

Hopkins University. Scientists there have developed two simple,

relatively inexpensive tests that use visual impairment as an

indicator of MS nerve damage.

One test measures thinning of the eye's retinal nerve with optical

coherence tomography, a machine now used for glaucoma screening. The

other test evaluates eyesight using an eye chart with letters that

are gray instead of the usual black. Nerve damage makes low-contrast

patterns difficult for MS patients to see.

" The more brain lesions, the worse the patient's visual score, "

explained Penn neuro-ophthalmologist J. Balcer. The new vision

tests already are being used in clinical trials of new drugs.