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Mon June 2, 2014

Pregnancy Hormone May Reduce Multiple Sclerosis Symptoms

Originally published on Tue June 3, 2014 9:30 am

For decades, women with multiple sclerosis have noticed that they tend to do better while they are pregnant. That has led to an experimental drug for the disease that's based on a hormone associated with pregnancy.

The hormone is a form of estrogen called estriol. It's abundant in a woman's body only when she is pregnant. Adding estriol to treatment with an existing MS drug cut relapses by 47 percent in a study of 158 women presented at the American Academy of Neurology meeting in April.

The result is "quite remarkable," says Rhonda Voskuhl, an author of the study and a neurologist at the University of California, Los Angeles. It suggests that estriol could greatly enhance the effectiveness of current MS drugs, Voskuhl says. Those drugs, which are designed to modulate the immune system, can cost up to $60,000 a year.

Multiple sclerosis is a disease that damages the myelin sheath covering nerve fibers. Researchers believe the damage is caused at least in part because the body's own immune cells begin attacking myelin. About 400,000 people in the United States have multiple sclerosis, with symptoms ranging from muscle weakness or paralysis to difficulty thinking.

The new research on estriol was inspired by decades of anecdotal reports from women like Melissa Sherak Glasser of Woodland Hills, Calif. Glasser is 41 now, but was diagnosed with MS when she was just 15.

She remembers putting one hand into a tub of bathwater to check the temperature and being surprised that it felt cold. "Then I put my other hand in and it was burning hot, and I thought, OK, something's wrong," she says.

An MRI scan showed that Glasser had MS. But Glasser didn't let the disease slow her down much. She was a cheerleader in high school, then went to college and graduate school and got married, despite relapses that caused temporary blindness, vertigo and difficulty walking.

When Glasser was in her mid-20s, she got pregnant. And one day, during an episode of morning sickness, she realized something surprising: Her MS symptoms had gone away. "I felt so horrible with all the pregnancy hormones, and I had to laugh," she says.

Glasser reported this to neurologists at UCLA who had been monitoring her MS since she was diagnosed more than a decade earlier. They weren't surprised. They'd heard stories like that before from women with MS. And pregnancy's effect on MS symptoms had been confirmed by a large scientific study in 1998.

So by the time Glasser became pregnant for the first time (she has four children now and was free of MS symptoms during all four pregnancies), Voskuhl and other researchers were already hard at work trying to identify the factor that was protecting pregnant women with MS. "If we could just figure it out, we would have an inroad to a major discovery," Voskuhl says.

The researchers knew that during pregnancy, a woman's immune system changes. "Pregnancy involves a fetus, which has half of the father's proteins on it," Voskuhl says. "So it's half foreign. In order to not reject that half-foreign fetus, the mother's immune system shifts."

Voskuhl figured that whatever was causing that shift was also protecting the woman's nerve fibers from MS. And she suspected a key factor was the hormone estriol.

So the researchers gave estriol to mice with multiple sclerosis and waited to see whether it would help them. "And indeed it did," Voskuhl says. "The mice were not paralyzed; they were walking around fine. It was just a dramatic reduction in their disease." Doses of the pregnancy hormone even worked in male mice.

Voskuhl was confident that estriol could help people with MS. But it took more than a decade to find out.

Drug companies weren't interested in estriol because it isn't a patented chemical, Voskuhl says. So she turned to the National Institutes of Health, the National Multiple Sclerosis Society and foundations, including one set up by the family of Melissa Sherak Glasser.

Ultimately, Voskuhl got the millions of dollars she needed to conduct a two-year trial of estriol in women who also were taking the widely used MS drug Copaxone. The success of that trial clears the way for a much larger study that can be submitted to the Food and Drug Administration for approval.

Glasser is confident that estriol will ultimately be approved as a treatment for MS and hopes to be one of the first people in the U.S. to get a prescription.

Copyright 2014 NPR. To see more, visit http://www.npr.org/.

Transcript

DAVID GREENE, HOST:

It's MORNING EDITION from NPR News. Good morning, I'm David Greene.

STEVE INSKEEP, HOST:

And I'm Steve Inskeep. We have a couple of stories on Your Health for this Monday morning. In a moment, we'll hear about a new treatment for severe heartburn that is changing some people's lives. First, we'll hear about an experimental drug for multiple sclerosis. That drug has its origins in an intriguing observation that women with MS tend to have fewer symptoms during pregnancy. NPR's Jon Hamilton reports.

JON HAMILTON, BYLINE: Multiple sclerosis usually strikes people in their 20s or 30s. Melissa Sherak Glasser was only 15 when the first symptoms appeared. She was about to take a bath.

MELISSA SHERAK GLASSER: I put my hand in the water to feel the temperature, and it was cold. And I thought, that's strange. And so then I put my other hand in, and it was burning hot. And I thought, OK, something's wrong.

HAMILTON: A MRI scan showed that Glasser had MS. It's a neurological disease that can cause everything from odd sensations, to muscle weakness, to trouble thinking. But Glasser didn't let the disease slow her down much.

GLASSER: I was a cheerleader, and I was very active. And so I, for some reason, always got symptoms on Fridays before games. And in my uniform, my mom would take me to the neurologist. He'd say, OK, just be careful. I would leave and go right to the game and cheer.

HAMILTON: Glasser went to college and to graduate school and got married. Along the way, she had a series of relapses. They caused temporary episodes of blindness, vertigo and difficulty walking. Then when Glasser, was in her mid-20s, she got pregnant. And one day during an episode of morning sickness, she realized something.

GLASSER: I was complaining, and I felt green. And I felt so horrible with all the pregnancy hormones, and I had to laugh. And everyone's like, what's wrong? And I'm like, this is my problem. Like, it's not, I can't walk. It's not I can't see. It's that I feel nauseous.

HAMILTON: Glasser's MS symptoms had disappeared, as they would during each of her four pregnancies. Neurologists often hear stories like that, and pregnancy's effect on MS was confirmed by a large scientific study in 1998. By that time, Glasser's doctors at the University of California, Los Angeles were trying to figure out what was protecting women like her. Rhonda Voskuhl, a neurologist, says this research was inspired by the things that Glasser and other pregnant women with MS had been reporting for years.

(SOUNDBITE OF ARCHIVED RECORDING)

RHONDA VOSKUHL: I saw it as a gift almost, a hint that there's something that is very important that's happening during pregnancy. And so if we could just figure it out, we would have an inroad to a major discovery.

HAMILTON: Multiple sclerosis appears to cause the body's own immune system to attack the myelin sheath covering nerve fibers. The body seems to mistake myelin for a foreign substance. But Voskuhl says during pregnancy, a woman's immune system changes.

VOSKUHL: Pregnancy involves a fetus, which has half of the father's proteins on it. So it's half-foreign. In order not to reject that half-foreign fetus, the mother's immune system shifts.

HAMILTON: Voskuhl figured that whatever was causing that shift was also protecting the nerve fibers. She was especially interested in a form of estrogen called estriol, which is only present in large quantities during pregnancy. Voskuhl gave estriol to mice with MS and waited to see whether it would help them.

VOSKUHL: And indeed it did, and indeed it was very dramatic. So the mice were not paralyzed. They were walking around fine, and it was just a dramatic reduction in their disease.

HAMILTON: Doses of estriol even worked in male mice, and Voskuhl was pretty sure the treatment would work in people. But it took more than a decade to find out. Drug companies weren't interested because estriol isn't a patented chemical. So Voskuhl turned to the National Institutes of Health, the National Multiple Sclerosis Society and foundations, including one set up by the family of Melissa Sherak Glasser. Ultimately, Voskuhl raised millions of dollars and was able to conduct a two-year trial of estriol in 158 women. All the women took an MS drug called Copaxone. Half of them also got estriol. Voskuhl says adding the pregnancy hormone made a big difference.

VOSKUHL: Within only one year of treatment, we saw a 47 percent reduction in relapses, which is quite remarkable.

HAMILTON: Voskuhl presented that finding at a scientific meeting just a few weeks ago, and now she's working with the FDA to design a much larger trial that could eventually allow estriol to be marketed to people with MS. In the meantime Glasser, who is 41 now, says she appreciates what Voskuhl has accomplished.

GLASSER: It was really actually amazing to watch her get the results that she got. She worked so hard for people with this disease.

HAMILTON: Glasser says she hopes to be one of the first MS patients in the U.S. to get a prescription for estriol. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.