VOSKUHL, RHONDA M.D.
The sex hormone estriol, released during pregnancy by the placenta, could be a powerful new treatment for multiple sclerosis. Doctors have known for years that women often experience a sharp drop in the disease's symptoms during the course of pregnancy, and a large trial is now getting underway to test estriol as a therapy for relapsing-remitting MS in women. People with relapsing-remitting MS have flare-ups that impair neurological function, followed by a partial or complete recovery period that is free of disease progression.
“By giving women 8 mg of estriol we are recreating the effect of pregnancy on MS,” says Rhonda Voskuhl, M.D., director of UCLA's Multiple Sclerosis Program and the lead researcher on the trial. “Of course, there is a lot going on in a woman's body during pregnancy, and estriol might work synergistically with some of those changes. But in our pilot study four years ago, we gave 8 mg of estriol to 10 non-pregnant women and found an 80 percent drop in inflammatory lesions in the brain. The women also showed substantial cognitive improvements. The results were pretty remarkable.”
Multiple sclerosis is an autoimmune disease of the central nervous system that attacks the tissue surrounding the brain's nerve fibers. This tissue, called myelin, can be compared to the insulation wrapped around an electrical wire. When the myelin is damaged, the nerve's ability to send signals to and from the brain is disrupted, resulting in problems with balance, memory, vision, and other functions.
Currently, anti-inflammatory drugs are used to lessen the symptoms and slow the progression of MS. But they must be given by injection—daily, weekly, or monthly, depending on the drug—and are expensive, costing between $12,000 and $24,000 a year.
“The beauty of estriol is that it can be given as a pill, not a shot,” Dr. Voskuhl says, “and it has a very good safety record behind it. Hundreds of thousands of women have taken it in Europe and Asia for relief of hot flashes. Unlike estradiol—another form of estrogen—estriol does not cause breast cancer. It can cause endometrial cancer, but that risk is very low if you take progesterone with it, which is how we are using it.” The fact that the estriol pill already exists, Dr. Voskuhl says, should also dramatically reduce the cost of MS treatment.
Produced by the placenta, estriol is virtually undetectable until pregnancy, when it progressively increases in the blood. Scientists think that its role is to suppress a woman's immune system so that the fetus will not be seen by the body as a “foreign invader.”
This special hormone might even provide a one-two punch against MS, both reducing the ability of immune cells to attack the brain and making the brain more resistant to damage if any immune cells do make it through. “If it does have neuroprotective benefits as well as anti-inflammatory effects,” Dr. Voskuhl says, “then it could be useful in treating other neurological diseases, such as Alzheimer's.”
Seven institutions from around the country will be involved in the two-year study. The investigators plan to recruit 150 women with relapsing-remitting MS who have not previously been treated or who have had less than three months of anti-inflammatory therapy. Participants will be given either estriol along with glatiramer (Copaxone), an MS drug currently in use, or a placebo with glatiramer. “That way, no one will receive less than the standard of care,” Dr. Voskuhl says. The team will then measure relapse rates over the course of the trial.
“We're testing estriol as an adjunct therapy, which is the first step,” Dr. Voskuhl says. If we show that estriol is useful as an add-on, then we could test it as a treatment on its own.
“One of the really exciting things about the study is that it was developed by researchers without a tie to the pharmaceutical industry and recommended for funding by the National Institutes of Health and the National MS Society, which is a non-profit. I think that speaks to the strength of the science.”
For more information about the trial, contact the UCLA Multiple Sclerosis program at 310-825-7313.