Using a chemical trigger to simulate pregnancy in mice with an MS-like disease, researchers were able to stop inflammation and reverse disability.
For decades, doctors have observed that pregnant women with relapsing/remitting multiple sclerosis (MS) appear to go into remission during their last trimester, when estrogen levels peak, only to have their symptoms return once they give birth.
Earlier studies on the use of estriol, the most common hormone in pregnancy, seemed promising for treating MS. But high doses of certain forms of estrogen, including estriol, can increase the risk of breast and uterine cancer. Hormones can also have “feminizing” side effects, posing an issue for men. The trick is to harness the benefits of estrogen while avoiding the risks.
Scientists at the University of California, Riverside, along with other research groups, have been looking for ways to trick the body into believing high levels of estrogen are present. Their goal is to find a drug that can switch on estrogen receptors and, in so doing, stop MS disease activity.
Using a chemical called indazole chloride (Ind-Cl), the group was able to switch on estrogen receptors in the oligodendrocytes of mice infected with a mouse model of MS. Oligodendrocytes are cells that make myelin, the protective layer that surrounds neurons in the brain. MS attacks and degrades myelin.
Even at the height of disease activity, the effects seen in the mice were amazing. Once the estrogen receptors were activated, the oligodendrocytes began to repair myelin and reverse damage to the nerves — the holy grail of MS research goals. And that wasn’t all.
The team also experimented on mice with nerve damage caused by things other than an autoimmune disease. They saw that the same myelin repair occurred. This shows that Ind-Cl may help reverse disability in people suffering from nerve damage due to traumatic brain injury and spinal cord injury as well.
During menopause, women produce less estrogen, and groups are working to see if drugs like Ind-CL might also treat menopausal symptoms.
The results of the new study were published in Proceedings of the National Academy of Sciences.
Because MS is an autoimmune disease, all of the disease modifying therapies (DMTs) used to treat it act to suppress the immune system, preventing destructive inflammation. But if the body’s defenses are too suppressed, opportunistic infections can take hold.
Since Ind-Cl selectively blocks inflammation of the nervous system, patients taking it will not be as immuno-suppressed as those taking most current DMTs, explained Seema Kaushalya Tiwari-Woodruff, an associate professor at Riverside and co-author of the study in an interview with Healthline
Repairing myelin — and reversing disability — is permanent, according to the study findings. So will patients have to take Ind-Cl regularly to keep inflammation from returning? “We are doing some experiments to assess that,” Tiwari-Woodruff said.
Although this study is promising, and demonstrates that Ind-Cl not only stops the disease process but also repairs myelin, whether that will translate into success in humans remains to be seen.
“We are testing four new analogues of Ind-Cl, followed by toxicology studies. Then we will file for [Investigational New Drug] approval,” said Tiwari-Woodruff. She estimates that the first human studies are two to five years away, “fingers crossed.”