xC G USzRkx WSW EzB Gh M

UNMC researchers participate in new drug study for multiple sclerosis, Crohn’s disease; results published in prestigious New England Journal of Medicine

Researchers at the University of Nebraska Medical Center were part of

whats being called a landmark international, 23-center study that tested

the safety of the drug natalizumab also known as Antegren. The drug may

benefit those with multiple sclerosis, a neurological disease and Crohns

disease, an intestinal disease.

Its a very promising medication that appears to slow down the disease

more than any of the other medications we have now, said Eliad Culcea,

M.D., UNMC assistant professor of neurology, who was part of the UNMC team.

It showed a significant decrease in the reduction of new lesions in the

brain, which means patients can be functional a longer period of time without

disease symptoms.

Results of the phase II, six-month preliminary study were published

in the Jan. 2 issue of the New England Journal of Medicine. UNMC enrolled

and evaluated some of its multiple sclerosis patients for the study, according

to Kathy Healey, nurse practitioner and coordinator of the study. UNMC

health professionals see 800 to 900 MS patients in its University Medical

Associates clinic.

Multiple sclerosis is a disease of the white matter of the brain and

spinal cord that affects the central nervous system. Symptoms of the disease,

such as weakness, tremors, loss of vision, cognitive changes, depression

and motor problems are episodic, meaning they come and go.

Frequency of symptoms vary patient-to-patient, anywhere from one short

episode a year, up to six-months long. With each flare of symptoms, the

number of brain lesions increase and the disease advances, according to

Mary Filipi, UNMC nurse practitioner who was involved in the study. If

left untreated, half of MS patients become wheelchair dependent within

15 years of disease onset.

Medication manages symptoms and acute attacks. However, the use of current

medications prescribed slow the disease by only 30 to 60 percent, according

to one of the UNMC study group members.

In Crohn’s patients, the study drug increased the rate of remission

and improved the patients’ quality of life.

In the randomized, double-blind trial, researchers studied 213 patients

with whats called relapsingremitting or relapsing secondary progressive

multiple sclerosis. At every 28 days over a six-month period, about one-third

of the patients received 3 mg of intravenous natalizumab per kilogram of

body weight, another third received 6 mg per kilogram and about a third

received placebo every 28 days for 6 months.

Currently, MS patients may receive injections anywhere from once a week

to every day. If this drug turns out to be effective, it would be very,

very helpful for patients to only receive one injection every 28 days,

said Ekaterini Markopoulou, M.D., assistant professor of neurology. If

it turns out that this drug can decrease the disease burden and resulting

disability in the long-term, it would be an important development in the

treatment of MS.

Researchers found marked reductions in the number of new lesions in

both groups receiving the drug: 9.6 per patient in the placebo group, as

compared with 0.7 in the group given 3 mg of the drug and 1.1 in the group

given 6 mg of the drug.  Twenty-seven of 71 patients in the placebo

group had relapses, as compared with 13 in the group given 3 mg of natalizumab

and 14 in the group given 6 mg of natalizumab.

The drug, a monoclonal antibody, works by blocking the adhesion of immune

cells to blood vessels and by inhibiting movement of immune cells from

the bloodstream into the brain. The drug is a new class of medication that

prevents inflammation.

The improvement of quality of life is one of the reasons why patients

take their medications, said Mary Filipi, UNMC nurse practitioner, who

also was part of the UNMC team. Wouldnt it be wonderful if patients could,

say, only receive an injection once a month or longer. People tell me they

want to forget they have this disease in between medications.

This is a difficult disease for patients to handle. You dont know

when episodes will hit you, what part of the body it will affect, how hard

it will hit, how long it will stay and how much deficit you will have when

it goes away. A teenaged athlete ended up having to periodically use crutches

because of the debilitating effects of MS. He told me hed rather have

had a stroke because he would then know how he would be from day-to-day.

The uncertainty he felt was heart-wrenching, Filipi said.

The drug companies that funded the study, Elan Pharmaceuticals and Biogen,

expect to seek approval for the drug at the end of 2003 in the United States

and Europe.

In Nebraska, about 110 to 140 cases per 100,000 people will occur, according

to the National Multiple Sclerosis Society. An estimated 1,600 to 1,800

Nebraskans have MS.

Life expectancy for people with MS has steadily improved. In 1890, the

disease was treated with herbs and bedrest, and life expectancy was five

years, according to the NMSS. By 1970, life expectancy rose to about 32

years, and today, people have a normal life expectancy.

Nationwide, it is estimated 250,000 to 350,000 people have multiple

sclerosis, which is often diagnosed between age 20 and 40. It is more common

among caucasians, particularly those of northern European ancestry, and

is more common in women than in men. Some of the potential causes of the

disease are believed to be viruses, as well as environmental, genetic,

and immune system factors.

Researchers say although the study found no major side effects to the

drug, a more extensive phase III study is now underway to study it effectiveness.

Our research team should be congratulated for contributing to such

a high quality international study that brings potentially unique, well-tolerated

and very effective therapy for multiple sclerosis, said Pierre Fayad,

M.D., Reynolds Centennial Professor and chairman of the UNMC Department

of Neurological Sciences.

Besides Drs. Culcea and Markopoulou, Healey and Filipi, other members

of the UNMC research team were: Agapito Lorenzo, M.D., and Sandy Roberts,

nurse. The late Jinan Al-Omaishi, M.D., led the UNMC study.