Taking the pregnancy hormone estriol along with their conventional medications helped patients with relapsing-remitting multiple sclerosis avoid relapses, according to results of a clinical trial.
The phase 2 randomized, placebo-controlled study was led by researchers at UCLA. Findings were published online Nov. 24 in the journal Lancet Neurology.
It is estimated that more than 2.1 million people are affected by MS worldwide. Approximately 85% of patients are diagnosed at onset with RRMS, the most common form of MS.
It long has been observed that during the second half of pregnancy, women with RRMS have reduced relapses. It is also during this period that the fetal placenta produces estriol, increasing the hormone levels in the blood. This protection during pregnancy also occurs in other autoimmune diseases such as psoriasis and rheumatoid arthritis.
The study’s lead author, Rhonda Voskuhl, MD, a professor and Jack H. Skirball Chair for Multiple Sclerosis in UCLA’s neurology department and director of UCLA’s Multiple Sclerosis Program, hypothesized the increased estriol in the blood might play a role in suppressing a woman’s immune system so the fetus is not rejected as being foreign. This temporary suppression of the immune system would be good for pregnant mothers with autoimmune diseases. Her team found treatment with estriol was protective in the MS model.
“The beauty of estriol is that it is not a shot and can be taken in pill form, and also that it’s not a new drug,” Voskuhl said in a news release. “It has decades of safety behind it. Also, current MS treatments are very complex to manufacture. These findings hopefully will pave the way for oral, safe treatments that are more widely accessible, since estriol is simple and naturally occurring.”
In RRMS, there are clear episodes of inflammatory activity, or relapses. During a relapse, there are new or worsening symptoms, accompanied by inflammatory lesions in the brain. Relapses usually are followed by remission, or improvement. However, there may be some residual symptoms, and after many years people with RRMS often transition to a progressive form of MS. During the progressive phase, there is gradual worsening of permanent disabilities and loss of brain volume or atrophy.
In the lab, the team discovered estriol reduces the ability of immune cells to attack the brain, while also making brain cells more resistant to damage if any immune cells do make it through. Specifically, researchers showed estriol treatment improved cognition and prevented atrophy of the cognitive region of the brain. It seems that during pregnancy, estriol can both suppress the immune system and protect the brain to avoid rejection of the fetus and to protect the developing fetal brain.
In 2002, Voskuhl completed the pilot study, in which 10 nonpregnant women with MS were given estriol, yielding a more than 70% drop in inflammatory lesions in the brain within six months of treatment.
In the phase 2 study launched in 2007 at UCLA and 15 other sites across the U.S., researchers enrolled 164 patients, with 83 allocated to the estriol group and 81 to the placebo group. Both groups continued their conventional medication, injectable glatiramer acetate. The team found the patients taking estriol had a third to a half as many relapses compared with those taking the placebo, with this improvement occurring beyond that provided by their conventional treatment. When estriol levels were the highest, researchers also found improved cognitive function and less atrophy of the brain area related to cognition. The treatment was well tolerated during the two years the volunteers took estriol, and the only significant side effect was irregular menstruation, according to the findings. To date, there is no FDA-approved treatment for MS that improves disabilities, according to the release.
These two trials were funded by the National Institutes of Health and the National Multiple Sclerosis Society. Other major funding was from the Conrad N. Hilton Foundation. Synthetic Biologics Inc. provided estriol and placebo for the multicenter trial and has licensed certain rights from UCLA.
Voskuhl hopes to see a phase 3 trial conducted to replicate these findings, which is necessary for FDA approval of estriol for MS.
“These findings are consistent with the hypothesis that increased concentrations of estriol during pregnancy might mediate, at least in part, the protective effect of pregnancy on relapse rates,” study authors wrote. “A phase 3 study of estriol in multiple sclerosis is needed to confirm these findings as well as to explore potential effects on disabilities.”