Female hormone estriol showing promise as MS therapy

Neurologist Rhonda Voskuhl led the study that showed a form of the hormone estrogen can reduce relapses in multiple sclerosis patients.
Neurologist Rhonda Voskuhl led the study that showed a form of the hormone estrogen can reduce relapses in multiple sclerosis patients. (UCLA)
Posted: June 05, 2014

A small study of the female hormone estriol has found it not only reduced the immune attacks of multiple sclerosis in women, but also improved their performance on mental tests - a benefit never demonstrated by the 10 approved MS drugs.

The two-year trial of 158 women, conducted at the University of Pennsylvania and 15 other centers, is a turning point for Rhonda Voskuhl, the neurologist who led the research.

She has spent 18 years working toward getting estriol approved as a therapy for the crippling neurological disorder, building on circumstantial evidence that MS flare-ups subside in pregnancy, the only time estriol is naturally abundant.

Voskuhl presented the latest data at the American Academy of Neurology's recent convention, and will soon submit it for review and publication in a journal.

"The beauty of estriol - and we've done a lot of work in animals showing this - is that it's not only anti-inflammatory but neuroprotective," said Voskuhl, head of the MS program at the University of California, Los Angeles. "It goes directly into the brain and binds to cells in the brain to protect them from damage. . . . None of the other drugs do that."

The Multiple Sclerosis Society, which underwrote the $5.6 million study with the National Institutes of Health, offered a cautious cheer.

"Neurodegeneration is an aspect of MS not addressed by current therapies," said Bruce Bebo, the society's associate vice president of discovery research. "Judgment needs to be reserved until we see the paper published in a journal. But I think this is very encouraging."

MS is a progressive disorder that damages the protective covering of nerves in the brain, spinal cord, and eyes. In the most common form of MS, attacks, or relapses, occur about once a year, producing patches of injured tissue than can be seen on MRI scans. A relapse is followed by a remission.

In the United States alone, MS affects more than 400,000 people - 300,000 of them female.

Decades of anecdotal reports from women such as Dawn Freney, 42, of West Chester, suggested estriol - a weak estrogen that does not have estrogen's cancer-promoting effects - might protect against MS.

Freney had six children in quick succession before being diagnosed with MS in 2009. Her neurologists estimated she'd had the disease for nine years, yet she had no disability - no muscle weakness or paralysis, no visual impairment, no cognitive decline. She still doesn't. Her worst symptom is fatigue.

"But I have six kids, so I'm always running around," said Freney, a technical writer for a health insurer.

Freney was part of the estriol trial at Penn. It will be several more months before she finds out whether she was taking estriol or a placebo.

"I can tell you I felt great while I was taking it," she said. "And my MRI scans have been stable; no growth, no shrinkage."

All women in the study took a standard MS drug called Copaxone, an injection that reduces the annual relapse rate by about 29 percent. Showing a decrease on top of that was a "difficult task," Voskuhl said, but estriol further cut the relapse rate by 47 percent.

Standard MS drugs, designed to modulate the immune system, can have severe side effects and cost up to $60,000 a year. Estriol, in contrast, has been used for 50 years in Europe and Asia to treat menopausal symptoms. While never approved by the Food and Drug Administration, it is available through U.S. compounding pharmacies that fill custom prescriptions.

The evidence that estriol prevents relapses was important, but the apparent neuroprotection presents new opportunities, Voskuhl said.

That's why she has launched a study at four sites, including Penn, to see whether estriol, used along with standard MS drugs, improves women's cognitive testing scores. (Search estriol Philadelphia at www.clinicaltrials.gov for more information.)

Meanwhile, Synthetic Biologics, the small Rockville, Md., firm that made the estriol pills under the brand name Trimesta, is optimistic about finding a deep-pocketed pharmaceutical partner for the final phase of development: the larger, definitive clinical trial needed for FDA approval.

Big drug companies are rarely interested in developing generic drugs for new uses because, under patent laws, the marketing rights are less exclusive than with a novel drug. But the apparent neuroprotective effects of estriol "are absolutely wonderful, especially with a drug that has no significant side effects," said Jeff Riley, Synthetic's president and CEO.

"There's a fair number of people who are courting us," he said.


mmccullough@phillynews.com

215-854-2720 @repopter

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