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Chemical Compound Decreases Effects of Multiple Sclerosis

A team of researchers led by biomedical scientist Seema K. Tiwari-Woodruff, an associate professor at the University of California, Riverside School of Medicine has identified a drug called indazole chloride (Ind-Cl) that could stimulate “remyelination,” the re-sheathing of the axons, restoring fast and uninterrupted flow of nerve impulses for patients with multiple sclerosis (MS). This is welcome news because currently available therapies are only partially effective in preventing the onset of permanent disability in MS patients. The report was published in December 2014 in the “Proceedings of the National Academy of Sciences”.

A release fro the university written by Iqbal Pittalwala explains that MS isan autoimmune disease of the brain and spinal cord that affects about 2.3 million people worldwide, with 400,000 of those patients in the United States. MS is more coming in women than men, and is most often diagnosed between the ages of 20 and 40, although the disease can occur at any age.

An unpredictable disease that disrupts the flow of information within the brain and between the brain and the body, MS is triggered when the immune system attacks the myelin sheath, the protective covering around the axons of nerve fibers. The “demyelination” that follows causes a disruption of nerve impulses. As the protective sheath – best imagined as the insulating material around an electrical wire – wears off, the nerve signals slow down or stop, and the patient’s vision, sensation and use of limbs get impaired. Permanent paralysis can result when the nerve fibers are completely damaged by the disease.

The release quotes Tiwari-Woodruff as saying, “This drug, which we administered on transgenic mice, 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.”

Tiwari-Woodruff explained that Ind-Cl is a chemical compound that stimulates an estrogen receptor, ERβ, in the body. As is well known, pregnant women with MS get near-complete relief from MS symptoms in their third trimesters. Estrogen levels, which are high at this time, have neuroprotective benefits, alleviating the MS symptoms. After the birth of the baby, estrogen levels plummet in the mother and the MS symptoms return.

“This readily suggests that estrogen could be given to MS patients, except that high levels of estrogen are linked to breast and uterine cancers,” said Tiwari-Woodruff, who joined UCR earlier this year. “Further, men would largely be reluctant to take estrogen due to its feminizing effects.”

Enter Ind-Cl, a small compound Tiwari-Woodruff has worked with for about two years. This structurally unique ligand turns on the body’s estrogen receptors without the negative effects of excessive estrogen.