| Small Trial Shows Daclizumab Add-On Therapy
Improves Multiple Sclerosis Outcome
A small clinical trial of patients with multiple sclerosis (MS)
who did not respond to interferon alone found that adding the human
antibody daclizumab improved patient outcome. Patients who received
the combined therapy had a 78 percent reduction in new brain lesions
and a 70 percent reduction in total lesions, along with other significant
clinical improvements. The trial was led by investigators at the
National Institute of Neurological Disorders and Stroke (NINDS),
a component of the National Institutes of Health. Findings will
appear in the Early Edition of the Proceedings of the National Academy
of Sciences¹ the week of May 24-28, 2004.
MS is a chronic disease marked by inflammation in the central nervous
system and development of lesions in the brain. Messages from the
brain to the body are interrupted as nerve fibers begin to lose
their protective coating of myelin, resulting in muscle weakness,
problems with vision and coordination, pain, and, in some patients,
cognitive impairments. Approximately 250,000 to 350,000 people in
the United States suffer from MS and about 200 new cases are diagnosed
by physicians each week. There is no cure for the disorder.
NINDS investigator Roland Martin, M.D., and colleagues studied
11 patients with either relapsing-remitting ² or secondary progressive ³
MS. Each patient was treated with beta interferon a naturally
occurring antiviral protein commonly used to treat MS. Patients
also received 7 treatments of daclizumab (a genetically engineered
human antibody that blocks the interleukin-2 receptor on immune
cells) administered intravenously at 2-week, and later, 4-week intervals.
Ten patients showed a reduction in both the severity and number
of brain lesions as demonstrated by magnetic resonance imaging.
The decrease in new lesions, as well as the total decrease in lesions,
occurred gradually over a 2-month span. Improvement was also seen
on a neurological rating scale and in a test of hand function. The
clinical improvement was unexpected in such a small trial, since
a larger number of patients is usually required to show clinical
effects. One patient with extremely high inflammation activity responded
initially to daclizumab but, as disease activity returned, was given
higher doses of the antibody and was excluded from final analysis.
"There is great interest now in new approaches and new therapies
for a disorder about which we know too little and have only moderately
effective therapies," said Dr. Martin. "The combined therapy
was well tolerated by all patients, with side effects that were
either mild or clearly not caused by daclizumab." He said the
therapy limits the activity of T-cells that attack the myelin coating
around the nerves, without shutting down the entire immune system.
"While these results are preliminary, this discovery offers
hope for thousands of patients with certain forms of MS. Findings
like this are helping us to better understand how this disease affects
the immune system, which offers hope for all MS patients,"
said Story C. Landis, Ph.D., NINDS director.
Further studies are needed to confirm the extent of the clinical
benefit of daclizumab on typical MS patients and determine whether
daclizumab is effective as a stand-alone therapy.
The study was a collaboration between the NINDS and its sister
agency, the National Cancer Institute (NCI). Thomas Waldmann, M.D.,
chief of the metabolism branch for NCI's Center for Cancer Research,
developed the antibody used in the trial.
Daclizumab (trade name Zenapax®) received FDA approval in 1997
for use in kidney transplantation.
The NINDS is a component of the National Institutes of Health within
the Department of Health and Human Services and is the nation's
primary supporter of biomedical research on the brain and nervous
This release will be posted on EurekAlert! at http://www.eurekalert.org
and on the NINDS website at http://www.ninds.nih.gov/news_and_events/index.htm.