Estrogen based treatment

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Estrogen based treatment

Postby NHE » Mon Sep 03, 2007 3:28 am

A New "Designer" Treatment for Multiple Sclerosis
Scientific American, August 28, 2007

Research shows that estrogen can be used to counteract nerve cell degeneration caused by MS without increased risks of breast and uterine cancers

Researchers have proposed a new treatment for multiple sclerosis (MS) that utilizes the hormone estrogen to stave off and even reverse some of the mysterious disease's debilitating symptoms without the dangerous side effects of some other hormone therapies.

MS is largely believed to be an autoimmune disease in which the immune system turns on healthy tissue—in this case in the brain and nervous system. Current treatments include medicines designed to suppress an overactive immune system and reduce inflammation, a first-line response of the immune system. Whereas Copaxone and other such drugs often improve some of the muscle weakness and movement issues associated with the condition, they do little to combat the accompanying neurodegeneration.

In recent years, researchers began focusing on the potential of estrogen in battling MS after observing that the disease went into remission during pregnancy. "Pregnant women had this beautiful effect…their estrogen levels went skyrocketing," says Seema Tiwari-Woodruff, an assistant professor of neurology at the University of California, Los Angeles, and lead author of a study on estrogen as a potential MS treatment published in Proceedings of the National Academy of Sciences USA. "As soon as they had the baby, the MS came back, and more drastically."

In the body, estrogen binds to two types of receptor proteins in cells: estrogen receptor α and estrogen receptor β. The former—often referred to as estradiol—is known to play a role in mediating the effects of tumor-causing agents—and a major risk of estrogen treatments is the increased risk for breast and uterine cancer in women. Estrogen receptor β has no known connection to tumor cell proliferation and, thusly, the research team believed it may present a better treatment option.

The U.C.L.A. team was able to target specific receptor proteins in a mouse model of multiple sclerosis by attaching receptor-specific compounds to estrogen. Young adult female mice (five to six weeks old) were given a compound that induced encephalomyelitis, an autoimmune condition similar to MS. Some of the infected animals immediately received estrogen targeted to the α receptor, whereas others received the β receptor–specific hormone.

The α group did not develop any MS symptoms; the animals did not display any movement effects or damage to nerves or to the myelin (protective sheath) on the cells' axons, which transmit information—in the form of electrical impulses—away from neurons. Tiwari-Woodruff notes that despite the heartening result, researchers are not sure exactly why it works. "We don't know if it was stopping inflammation," she says, "or directly stopping the degeneration of neurons and axons."

The mice that received estrogen targeted to the β receptor initially developed signs of MS, including difficulty maintaining balance and a generally slower gait. The scientists say there was inflammation throughout these animals' central nervous systems. But some 20 days later, these mice began to show improvements in motor control, eventually regaining the ability to walk normally—and despite inflammation there was no neurodegeneration, which typically occurs at this stage of the disease. "This is the first time," she says, "a hormone treatment has been described [that works] without touching the inflammation part" of the equation.

Targeting the α receptor may provide a more thorough treatment, but researchers say it is not clear that its benefits outweigh the increased cancer risk that accompanies it. The gradual β receptor treatment offers the opportunity to protect an MS patient from neurodegeneration; supplementing it with an anti-inflammatory drug could counter swelling, yielding an all-around safer therapeutic option for women as well as for men.

"The β receptor is not one of the receptors that causes breast growth and all the feminine side effects" Tiwari-Woodruff says, "so this could potentially be given to men, too." She adds that the U.C.L.A. team will now try out the β receptor–targeted estrogen in a male mouse model. Next up: human trials if those go well.

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HRT and Neuroprotection

Postby Shayk » Mon Sep 03, 2007 5:59 pm

NHE

Thanks for posting this. I remain optimistic about the potential of "estrogen" for everyone and am glad to see it's being pursued.

There was a presentation at ACTRIMS 2007 (It's on page 46 of the pdf.) that seems to suggest that the neuroprotective properties seen in mice might actually translate to people. :D

P20 HRT contributes to neuronal health in postmenopausal women with MS

K Fuchs1, AP Haley2, MD Goldman1, J Knight-Scott3 and VI Simnad1

Results: The groups were comparable in age (mean 50.5 years, p 0.07) and disability level as assessed by the MS Functional Composite (mean z 0.08, p 0.72).

[b]There was a significant difference (p 0.015) in the NAA/Cr ratio between the women on HRT (1.91 0.39)and the women not on HRT [/b](1.41 0.32).

When age, level of disability, and use of immunomodulatory therapy were used as covariates in the statistical analysis, the signicant difference between the groups remained.

Conclusions: In this small sample, we demonstrated that use of exogenous estrogen may contribute to neuronal health as measured by MRS.


I think the NAA/Cr ratio is used as a marker for the loss of neurons and axons. Presumably, given the conclusion, women on HRT lost fewer axons and neurons than women not on HRT. And, even though the sample size was small (8 on HRT, 8 not on HRT) the findings were "significant."

Unfortunately, the info doesn't indicate if the HRT in this case was estrogen only or estrogen + progesterone but I still think it's noteworthy that the neuroprotection apparently translated to people with MS. 8)

Take care all

Sharon

btw--I'm sure you all know I found this statement really interesting.
"This is the first time," she says, "a hormone treatment has been described [that works] without touching the inflammation part" of the equation.
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Re: Estrogen based treatment

Postby NHE » Wed Sep 05, 2007 4:18 pm

For those interested, here is link to the journal abstract for this paper.

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