Sep. 24, 2002 A hormone common in pregnant women shows promise as an easily administered treatment for people with early-stage multiple sclerosis (MS). A new study by UCLA neuroscientists shows for the first time in humans that estriol in oral tablet form can decrease the size and number of brain lesions, and increase protective immune responses in patients with relapsing remitting MS. The results of the Phase I clinical trial led by Dr. Rhonda Voskuhl, an associate professor of neurology at the David Geffen School of Medicine at UCLA and the study's principal investigator, appear in the October edition of the Annals of Neurology. Previous research has found similar results in pregnant women and animals with early-stage MS.
"I am excited by the prospect of finding an easily administered treatment for MS based on a naturally occurring phenomenon in pregnancy. At present the only approved treatments are anti-inflammatory drugs administered with injections," said Voskuhl, also a research scientist at UCLA's Brain Research and Neuropsychiatric institutes. "Our findings also hold promise for finding new treatments for a host of other autoimmune disorders that improve during pregnancy, such as rheumatoid arthritis."
MS is a chronic disabling disease that affects one in 10,000 people. Symptoms typically appear between age 20 and 30. The progressive neurological disorder is most common among individuals of northern European ancestry and occurs two to three times as often in women than in men. Symptoms range from numbness in the limbs to paralysis to blindness.
Researchers believe the cause is polygenetic, with individuals who contract the disease inheriting a specific combination of genes from both mother and father. Symptoms develop when the immune system becomes overactive and attacks neurons, or brain cells, by stripping away a conductive coating. Once the coating is stripped away, the neurons don't conduct the brain's electrical signals as well.
The early phase of the disease, or relapsing remitting MS, is characterized by inflammation in the brain with milder neurological symptoms that come and go. After about 10 years, the disease typically moves into the secondary progressive phase, with chronic, disabling symptoms increasing and taking hold as the brain atrophies. Anti-inflammatory injections are effective for only relapsing remitting MS.
"MS doesn't cut life short, it kills the quality of life," Voskuhl said. "Early treatment is crucial to preventing disabling symptoms. Finding an easily administered oral treatment is important, in part, because patients are less likely to delay treatment if it involves a pill rather than weekly or daily shots."
Estriol is a weak form of estrogen made by the fetal placental unit and appearing in appreciable amounts only in pregnant women. The hormone is used widely throughout Europe and Asia to treat symptoms of menopause but is not approved in the United States for hormone replacement therapy because it does not prevent osteoporosis.
The clinical trial involved 12 women, six with relapsing remitting MS and six with secondary progressive. Ten of the patients completed the trial, including all six with relapsing remitting MS. Periodic Magnetic Resonance Imaging (MRI), immune system tests and cognitive tests were conducted for each patient during a six-month pretreatment period, a six-month estriol treatment period, a six-month post-treatment period and a four-month treatment extension.
Among relapsing remitting patients treated with estriol, researchers found a significant decrease in the number and size of inflammatory brain lesions, an increase in protective immune response and an improvement in cognitive test scores. When estriol treatment ended, the lesions increased to pretreatment levels. When treatment was reinstated, the lesions again significantly decreased. Researchers found no significant improvement in lesions or immune response among the four secondary progressive MS patients who completed the clinical trial.
"Based on these results, a larger, placebo controlled trial of estriol is warranted in women with relapsing remitting multiple sclerosis," Voskuhl said. "If larger studies confirm the benefits of estriol treatment, further studies for longer periods of time will be needed to determine whether estriol can decrease relapse rates and disabling symptoms."
### The study was funded by the National Multiple Sclerosis Society, the National Institutes of Health and the Sherak Family Foundation Fund for Multiple Sclerosis.
Other UCLA researchers involved in the study were Nancy L. Sicotte, Stephanie M. Liva, Rochelle Klutch, Paul Pfieffer; Seth Bouvier and Sylvia Odesa, all of the Department of Neurology, and T. C. Jackson Wu of the Department of Obstetrics and Gynecology.
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