Researchers Identify Chemical Compound That Decreases Effects of Multiple Sclerosis

UC Riverside-led mouse study shows the ligand indazole chloride improves motor function, imparting therapeutic benefits even when treatment is initiated at the peak of disease

By Iqbal Pittalwala on December 1, 2014

Seema Tiwari-Woodruff is an associate professor of biomedical sciences at the UC Riverside School of Medicine. Photo credit: I. Pittalwala, UC Riverside.

RIVERSIDE, Calif. Multiple sclerosis (MS), an autoimmune disease of the brain and spinal cord, affects about 2.3 million people worldwide (400,000 in the United States). Affecting more women than men, it can be seen at any age, although it is most commonly diagnosed between the ages of 20 and 40.

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 patients vision, sensation and use of limbs get impaired. Permanent paralysis can result when the nerve fibers are completely damaged by the disease.

Given such debilitating effects, an aggressive search is on among scientists to find a cure for MS. Currently available therapies are only partially effective, however, in preventing the onset of permanent disability in MS patients. What would be immensely helpful is a drug that could minimize the degeneration of axons, thus reducing the rate and degree of MS progression. Better still would be if this drug could stimulate remyelination, the re-sheathing of the axons, restoring fast and uninterrupted flow of nerve impulses.

Seema Tiwari-Woodruff (left) is seen here with two of her lab staff members, Leonardo Martinez-Torres (center) and Jonathan Hasselmann. Photo credit: I. Pittalwala, UC Riverside.

Now a team of researchers, led by a biomedical scientist at the University of California, Riverside, reports in this weeks issue of the Proceedings of the National Academy of Sciences that it has identified just such a drug in the lab: indazole chloride (Ind-Cl).

This drug, which we administered on transgenic mice, can potentially halt the symptoms and reverse ongoing motor deficit due to MS, said Seema K. Tiwari-Woodruff, an associate professor in the UC Riverside School of Medicine whose lab led the study. 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, ER, 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.

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Researchers Identify Chemical Compound That Decreases Effects of Multiple Sclerosis