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 is an autoimmune disorder and central nervous system disease. In MS, the immune system attacks the myelin sheath, which normally wraps around nerve fiber axons and helps them to transmit information. The damage to myelin that occurs in MS can cause unpredictable impairment of movement, vision, and sensation. The disease is typically diagnosed between the ages of 20 and 40, and is seen more often in women than in men. About 2.3 million people worldwide (300,000 to 400,000 in the United States) are diagnosed with MS.
In this study, Ind-Cl was given to mice with an experimental form of MS, known as chronic experimental autoimmune encephalomyelitis (EAE). The drug improved movement and reduced cellular effects that are caused by MS, specifically inflammation and immune system responses. Myelination of axons also increased.
“We found that remyelination occurred more efficiently in such mice after they were given Ind-Cl,” stated Seema K. Tiwari-Woodruff, associate professor in the UC Riverside School of Medicine and leader of the study. “This means Ind-Cl works in two ways: through the immune system in terms of reducing brain and spinal cord inflammation, and directly by remyelinating the axons. This makes it an extremely promising drug.”
She further remarked “This drug . . . can potentially halt the symptoms and reverse ongoing motor deficit due to MS. Our study shows that Ind-Cl can remyelinate axons which have gotten injured not just in MS but also traumatic brain injury and spinal cord injury.”
Interestingly, Ind-Cl acts somewhat like estrogen in the body, since it binds to specific estrogen receptors. Pregnant women with MS experience dramatic decreases in MS symptoms in their third trimesters when estrogen levels are high. After pregnancy, estrogen levels decline in the mother and the effects of MS resume.
Tiwari-Woodruff noted “This readily suggests that estrogen could be given to MS patients, except that high levels of estrogen are linked to breast and uterine cancers. Further, men would largely be reluctant to take estrogen due to its feminizing effects.”
For this reason, a drug that acts like estrogen but does not have all of estrogen’s effects, such as Ind-Cl, could be a better option. Other versions of the medication known as analogues, are in development by John A. Katzenellenbogen, an organic chemist at the University of Illinois at Urbana-Champaign and a coauthor on the research paper who also developed Ind-Cl. His research group will further test four Ind-Cl analogs on mice with experimental MS.
According to Tiwari-Woodruff “We expect some of these analogs will soon go to clinical trial.”