A hormone common in pregnant women showspromise as an easily administered treatment for people with early-stagemultiple sclerosis (MS). A new study by UCLA neuroscientists shows for thefirst time in humans that estriol in oral tablet form can decrease the size andnumber of brain lesions, and increase protective immune responses in patientswith relapsing remitting MS.
The results of the Phase I clinical trialled by Dr. Rhonda Voskuhl, an associate professor of neurology at the DavidGeffen School of Medicine at UCLA and the study's principal investigator,appear in the October edition of the Annals of Neurology. Previous research hasfound similar results in pregnant women and animals with early-stage MS.
"I am excited by the prospect of finding aneasily administered treatment for MS based on a naturally occurring phenomenonin pregnancy. At present the only approved treatments are anti-inflammatorydrugs administered with injections," said Voskuhl, also a research scientist atUCLA's Brain Research and Neuropsychiatric institutes. "Our findings also holdpromise for finding new treatments for a host of other autoimmune disordersthat improve during pregnancy, such as rheumatoid arthritis."
MS is a chronic disabling disease thataffects one in 10,000 people. Symptoms typically appear between age 20 and 30.The progressive neurological disorder is most common among individuals ofnorthern European ancestry and occurs two to three times as often in women thanin men. Symptoms range from numbness in the limbs to paralysis to blindness.
Researchers believe the cause ispolygenetic, with individuals who contract the disease inheriting a specificcombination of genes from both mother and father. Symptoms develop when theimmune system becomes overactive and attacks neurons, or brain cells, bystripping away a conductive coating. Once the coating is stripped away, theneurons don't conduct the brain's electrical signals as well.
The early phase of the disease, orrelapsing remitting MS, is characterized by inflammation in the brain withmilder neurological symptoms that come and go. After about 10 years, thedisease typically moves into the secondary progressive phase, with chronic,disabling symptoms increasing and taking hold as the brain atrophies. Anti-inflammatoryinjections are effective for only relapsing remitting MS.
"MS doesn't cut life short, it kills thequality of life," Voskuhl said. "Early treatment is crucial to preventingdisabling symptoms. Finding an easily administered oral treatment is important,in part, because patients are less likely to delay treatment if it involves apill rather than weekly or daily shots."
Estriol is a weak form of estrogen made bythe fetal placental unit and appearing in appreciable amounts only in pregnantwomen. The hormone is used widely throughout Europe and Asia to treat symptomsof menopause but is not approved in the United States for hormone replacementtherapy because it does not prevent osteoporosis.
The clinical trial involved 12 women, sixwith relapsing remitting MS and six with secondary progressive. Ten of thepatients completed the trial, including all six with relapsing remitting MS.Periodic Magnetic Resonance Imaging (MRI), immune system tests and cognitivetests were conducted for each patient during a six-month pretreatment period, asix-month estriol treatment period, a six-month post-treatment period and afour-month treatment extension.
Among relapsing remitting patients treatedwith estriol, researchers found a significant decrease in the number and sizeof inflammatory brain lesions, an increase in protective immune response and animprovement in cognitive test scores. When estriol treatment ended, the lesionsincreased to pretreatment levels. When treatment was reinstated, the lesions againsignificantly decreased. Researchers found no significant improvement inlesions or immune response among the four secondary progressive MS patients whocompleted the clinical trial.
"Based on these results, a larger, placebocontrolled trial of estriol is warranted in women with relapsing remittingmultiple sclerosis," Voskuhl said. "If larger studies confirm the benefits ofestriol treatment, further studies for longer periods of time will be needed todetermine whether estriol can decrease relapse rates and disabling symptoms."
The study was funded by the NationalMultiple Sclerosis Society, the National Institutes of Health and the Sherak Family Foundation Fund forMultiple Sclerosis.
Other UCLA researchers involved in thestudy 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.
UCLA Department of Neurology: neurology.medsch.ucla.edu/
UCLA Brain Research Institute: www.bri.ucla.edu/
UCLA Neuropsychiatric Institute: www.npi.ucla.edu/
David Geffen School of Medicine at UCLA: www.medsch.ucla.edu/
Annals of Neurology: www.aneuroa.org/annals.htm