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CMSC INforMS: UCLA researchers work to advance treatment targeting source of multiple sclerosis

Wednesday, May 15, 2019  
Posted by: Elizabeth Porco
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UCLA researchers are developing the first multiple sclerosis treatment that could target the cause of the disease, instead of simply treating its symptoms.

Multiple sclerosis is an autoimmune disease in which the fatty coating of nerve cells, called the myelin sheath, is broken down by one’s immune system. MS causes a wide range of symptoms such as blindness and limb weakness. A study published in the journal “Proceedings of the National Academy of Sciences of the United States” found that the cause of these symptoms could be alleviated with estrogen treatments.

Rhonda Voskuhl, the director of the UCLA Multiple Sclerosis Program and Clinic who led the study, said current MS treatments available to patients only mitigate the inflammation of nerve cells caused by the loss of myelin.

“The myelin is like the rubber coating on a wire, and when you strip it off, it doesn’t conduct very well,” Voskuhl said. “Currently, all the treatment reduces inflammation … but what they don’t do is repair.”

As opposed to simply treating inflammation, Voskuhl used estrogen to regenerate myelin by stimulating the production of cholesterol, the main component of myelin. Voskuhl said adults have trouble repairing damage caused by the loss of myelin, but increased cholesterol in the brain helps aid the process.

“The myelin is made when the baby’s brain is developing,” Voskuhl said. “We could repair (the myelin) by bringing back some of the mechanisms that are there during developmental myelin formation.”

Voskuhl said she discovered estrogen’s potential as a treatment after observing how women’s MS symptoms decreased during pregnancy due to increased levels of the hormone. Researchers determined which type of estrogen would be most effective using the process of elimination, said Noriko Itoh, a coauthor of the study and staff research associate in UCLA’s neurology department.

Estriol, a type of estrogen produced by the fetal placenta, was found to act specifically on the brain cells that produce myelin through an estrogen receptor called beta, which relays signals from the body into the cell that trigger a change in gene expression.

“A lot of the protective properties in the brain (use) receptor beta,” Voskuhl said. “We targeted it, and showed that it was actually on these cells that make myelin, which are called oligodendrocytes.”

Voskuhl said estrogen is much less toxic and more affordable than other MS treatments. Although estrogen has been linked to an increased risk of breast cancer, estriol is safer than the estrogen found in birth control pills, which can increase the risk of blood clots, Voskuhl said.

“The risk-benefit ratio is quite good when we consider what multiple sclerosis patients have to take for their disease,” Voskuhl said. “(Our treatment) is so safe, that even a lot of healthy people take estrogen.”

Macy Matsukawa, a co-author of the study and fourth-year biology student, said roughly 1 million people in the U.S. have been diagnosed with MS. Patients who have more severe symptoms may lose their jobs due to the development of disabilities, Itoh said. New treatments that increase myelin repair could improve the lives of those affected by the disease, Matsukawa said.

“By having a cell-specific and region-specific treatment for these patients, we can provide more improvement in their daily lives,” Matsukawa said.

Voskuhl said the researchers have conducted a series of small clinical trials with patients that have delivered promising results. She said she is hoping to expand the next trial to include 1,000 patients to confirm that estrogen can be used to repair myelin.

“It would be a major breakthrough if we could use this hormone to repair the brain, and more specifically cause remyelination,” Voskuhl said.

Daily Brun

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