Current therapies for relapsing-remitting MS prevent relapses and slow disability progression by reducing inflammation; however, they are unable to restore myelination or reverse damage.
Researchers at the University of California, Riverside (UCR), found that indazole chloride, a synthetic compound that acts on 1 form of the body’s estrogen receptors previously shown to reduce MS symptoms in mouse models, can treat the loss of myelin in the disease.
Loss of myelin causes the nerve signals to slow down or stop, affecting vision, movement, memory, and more. When remyelinating the damaged axons, nerve impulses travel faster than before and decrease disability caused by MS. The UCR researchers determined that the change in the immune system provides a protective shield for oligodendrocytes, which can help potentially prevent myelin damage and even reverse it.
According to the researchers, indazole chloride helps to reduce the “bad inflammation” while promoting “good inflammation” by strengthening the production of a molecule called CXCL1, which makes oligodendrocytes resistant to bad inflammatory signals. The potential neuroprotective benefits from the presence of CXCL1 could have implications for improved MS therapies, the study noted.
“As a potential therapy for the treatment of multiple sclerosis, indazole chloride may represent the first in a novel class of drugs capable of reducing disability burden in patients with multiple sclerosis,” Seema Tiwari-Woodruff, PhD, study author, associate professor of biomedical sciences in the School of Medicine, said in a press release.
Dr Tiwari-Woodruff noted that their report aims to eventually understand the mechanisms of drugs such as indazole chloride.
Indazole chloride is a ligand that stimulates ERb, an estrogen receptor in the body, but does not produce the negative adverse effects of estrogen therapy. The researchers indicated that indazole chloride may have therapeutic benefits for other autoimmune diseases as well.
The researchers are also screening chemically similar analogs of indazole chloride for more efficacious and safe therapy. The research was supported by grants from the National Institutes of Health and the National Multiple Sclerosis Society.
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1. Karim H, Kim SH, Lapato AS, et al. Increase in chemokine CXCL1 by ERb ligand treatment is a key mediator in prompting axon myelination. Proceedings of the National Academy of Sciences. 2018. https://doi.org/10.1073/pnas.1721732115.
2. Chemical Compound Produces Beneficial Inflammation and Remyelination That Could Help Treat Multiple Sclerosis [news release]. UCR’s website. https://ucrtoday.ucr.edu/53712. Accessed May 30, 2018.