Innovative compound offers novel therapeutic approach to treat multiple sclerosis

Multiple sclerosis is an autoimmune disease that affects more than 2.3 million people worldwide. This debilitating disease periodically prevents communication between the brain and other parts of the body, resulting in symptoms ranging from numbness and tingling in the arms and legs to blindness and paralysis. Although treatments are available to relieve inflammation, no treatment exists to protect neurons or repair the degraded myelin sheath that normally surrounds the nerves.

Previous studies have shown that estrogens and estrogen-related compounds reduce inflammation and disability-type multiple sclerosis in mice. At first glance, these treatments look promising, but they cause a host of side effects, ranging from feminized mice to increased risk of cancer, heart disease and stroke. An interdisciplinary team of scientists is inspired by this approach with a new concept that alleviates side effects while alleviating symptoms.

In an article published on January 24 in Scientific reportsSeema Tiwari-Woodruff, an badociate professor of biomedical sciences at the University of California's School of Medicine, Riverside, and her colleagues describe their efforts to create new forms of estrogen receptors. Their work shows that these new compounds offer the protective effects of estrogen without the unpleasant side effects.

"Multiple sclerosis is a complicated disease that presents multiple aspects of the disease: inflammation, demyelination and neuronal death," said Tiwari-Woodruff, a corresponding author of the journal. "We think we've created a drug that really does two things, modulating inflammation and allowing axon remyelination, and no other drug on the market can do both of these things at the same time."

Tiwari-Woodruff has turned to colleagues at the University of Illinois Urbana-Champaign, or UIUC, to develop new forms, or the like, based on the parent molecule, chloroindazole.

John Katzenellenbogen, research professor, and Sung Hoon Kim, a researcher at the UIUC Department of Chemistry, began by adding various chemical groups to the backbone of the parent molecule to produce 20 badogues. These functional badogues have similar physical, chemical, biochemical and pharmacological properties as chloroindazole, but interact with estrogen receptors in a slightly different manner.

"Our question was: can we modify the parent compound to produce a better drug that would be more effective in human testing," said Tiwari-Woodruff.

Tiwari-Woodruff and his team examined these chloroindazole badogs in cell culture to identify the most promising candidates. They identified two ¾IndCl-o-Cloro and IndCl-o-Methyl. Moving on to preclinical testing, they examined the therapeutic effect of both badogues with the help of a mouse model (experimental autoimmune encephalomyelitis) mimicking the symptoms of multiple sclerosis. They found that these compounds reduced disability better and encouraged remyelination over the parent compound without any significant side effects.

According to Tiwari-Woodruff, this family of compounds has potential for future therapeutic development, particularly for the protection of neurons and nerve coverage of myelin. She points out that more work is needed to explore the effect of badogues at different doses and administered at different stages of the disease.

The scientists participating in the study have patented the badogs and hope to begin pharmacological and toxicity tests in the near future. After these tests, the drug can be evaluated in clinical trials to determine the safety and efficacy of treatment for multiple sclerosis in men. Tiwari-Woodruff hopes that these new compounds can be marketed in the coming years.

"The most amazing part of the study is that these new badogs of a known estrogen modulator, chloroindazole, are superior in the treatment of the murine model of multiple sclerosis", a- she declared.