estrogen

Hormonal changes over time — and especially those around menopause — are often associated with disability worsening in multiple sclerosis (MS) patients, which suggests that sex-specific hormone therapies may be useful in MS treatment. Burcu Zeydan, MD, assistant professor of neurology and radiology at Mayo Clinic, provided an overview…

The use of oral contraceptives does not increase the risk of a second attack of symptoms or the progression of disability in women with clinically isolated syndrome (CIS) or early stage multiple sclerosis, a study demonstrated. Notably, the researchers also “did not find a protective effect on disability…

Editor’s note: The Multiple Sclerosis News Today news team is providing in-depth and unparalleled coverage of the virtual ACTRIMS Forum 2021, Feb. 25–27. Go here to see all the latest stories from the conference. At the ACTRIMS Forum 2021, Rhonda Voskuhl, MD, a neurology professor at the University…

An estrogen-based therapy, called indazole chloride (IndCl), was shown to protect against optic nerve damage in a mouse model of multiple sclerosis (MS), a study reported. IndCl may help to improve vision in people with the disease, but…

Throughout 2019, Multiple Sclerosis News Today brought you daily coverage of the latest scientific findings, treatment developments, and clinical trials related to multiple sclerosis (MS). We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2020. Here are the top 10 most-read articles of…

Giving estrogen to two different adult mouse models of multiple sclerosis (MS), including the experimental autoimmune encephalomyelitis (EAE) model, promoted remyelination, a new study shows. Exposure to the hormone affected gene activity in oligodendrocytes, tricking them into producing myelin (the fatty substance that protects nerve cells, and that is destroyed…

Two newly identified variants of the known pharmaceutical agent chloroindazole showed significant anti-inflammatory and neuroprotective benefits in a mouse model of multiple sclerosis, a new study shows. Multiple sclerosis is an autoimmune, demyelinating disease of the central nervous system with no known cause or cure. Patients with MS characteristically show loss of the myelin sheath, a protective coat in nerve cells that helps increase cell-to-cell signaling. Several studies have suggested that estrogens — a type of hormone — are beneficial to the functioning of the central nervous system, and help regulate the immune system. Thus, they are attractive candidates for the treatment of MS. However, despite their potential to treat MS, estrogen-based therapies can have several undesirable side effects, such as feminizing male recipients and increasing the risk of developing breast and endometrial cancers in females. Interestingly, estrogens work by binding and activating two different types of receptors: the estrogen receptor (ER)α and ERβ. The cancer-inducing effects of estrogens are mediated mainly through estrogen receptor ERα. Hence, therapies that specifically target ERβ can bypass these deleterious effects. Chloroindazole (IndCl), a pharmaceutical agent, has up to 100-fold relative binding affinity for ERβ over ERα. IndCl has been shown previously to have beneficial effects on modulating the immune system and the central nervous system, and inducing myelination of nerve cells in mouse models of MS. Furthermore, IndCl and other ERβ-activating agents directly support the growth, differentiation (maturation), and overall myelination activity of oligodendrocytes, which are the nerve cells that produce the myelin sheath. Therefore, in order to optimize the benefits of IndCl, researchers developed and screened seven novel IndCl analogues for their ability to promote oligodendrocyte survival, growth, and differentiation. These analogues have a molecular structure closely similar to that of IndCl, but interact with estrogen receptors in subtly different ways. Among these seven compounds, researchers found two analogues — IndCl-o-chloro and IndCl-o-methyl — that stimulated growth and differentiation similar to the original IndCl. Next, researchers evaluated the benefits of these compounds in a mouse model of MS — the experimental autoimmune encephalomyelitis (EAE) mouse model — to determine whether they could alter the disease course, white matter pathology (level of demyelination), and inflammation. Results indicated that both compounds “ameliorated disease severity, increased mature OLs [oligodendrocytes], and improved overall myelination in the corpus callosum and white matter tracts of the spinal cord,” researchers wrote. Corpus callosum is a thick band of nerves that connect the left and right side of the brain. White matter tracts connect the cortex (the largest part of the brain) with other areas in the central nervous system. These beneficial effects were accompanied by a reduced production of the toxic, inflammatory molecules interferon-γ and CXCL10. Additionally, IndCl-o-methyl also reduced the levels of peripheral interleukin (IL)-17, a molecule that strongly induces inflammation. Furthermore, IndCl and both analogues upregulated the expression of a compound called CXCL1, which is associated with increased production of oligodendrocytes. Not only were these two newly identified compounds equivalent to IndCl, but the two analogues performed better in reducing disability and encouraging remyelination than the original compound, and without any obvious side effects. “The o-Methyl and o-Chloro IndCl analogues represent a class of ERβ ligands that offer significant remyelination and neuroprotection, as well as modulation of the immune system; hence, they appear appropriate to consider further for therapeutic development in multiple sclerosis and other demyelinating diseases,” the researchers concluded. “We believe we created a drug that does two things really well, modulating inflammation and allowing axon remyelination. No other drug on the market can do these two things simultaneously,” Seema K. Tiwari-Woodruff, said in a press release written by Stacy Kish. Tiwari-Woodruff is the study's lead author. “The most amazing part of the study is that these new analogues of a known estrogen modulator, chloroindazole, are superior in treating mouse model of multiple sclerosis,” she added. The team has patented the analogues, and hopes to begin further pharmacological and toxicity studies soon.

A team of researchers at the University of California, Riverside, along with other collaborators, have identified a drug associated with estrogen, indazole chloride (Ind-Cl), that blocks the effects of multiple sclerosis (MS). The findings were reported December 1st in the Proceedings of the National Academy of Sciences. MS…