Researchers have identified a potential therapeutic target for the treatment of multiple sclerosis. In their latest study, which was conducted using an experimental mouse model of MS, they explored the role of connexin 43, a protein involved in cellular communication and cardiac function, and examined whether targeting this protein with specific blockers could improve MS symptoms.

In a 2013 study, researchers from Kyushu University, found that the production of Cx43 was increased in supportive cells called astroglia, near MS lesions. Cx43 is essential for cell-to-cell signaling and plays a key role in modulating the immune system. The researchers therefore hypothesized Cx43 could play a pivotal role in promoting neuroinflammation — a process where the immune response is triggered to fight off infection or heal damaged tissue — in the context of MS, ultimately leading to demyelination.

A new study by Kyushu University researchers, in collaboration with researchers from the International University of Health and Welfare, adds further support to the hypothesis that Cx43 plays a key role in causing MS. The study revealed a drug called INI-0602, which effectively ‘plugs’ and blocks Cx43 channels, markedly improved MS symptoms in mice. The researchers conducted an extensive series of experiments in an experimental mouse model of MS and in cultured astroglia cells from the mouse model, to understand the effects of Cx43 blockade. The results of these tests and analyses were consistent, suggesting that INI-0602 could not only suppress the overproduction of Cx43 in astroglia, but also mitigate many of the hallmark features of MS, including demyelination and excessive immune cell infiltration into the nervous system.

By delving further into the mechanisms underlying these results, the team found that INI-0602 led to improved symptoms by regulating immune processes. More specifically, treatment with this compound reduced the levels of proinflammatory cytokines — proteins produced by immune cells that trigger the immune system — and increased those of anti-inflammatory cytokines in the cerebrospinal fluid. The drug also altered calcium signaling in astroglia, limiting their ability to promote inflammation. Together, these effects reduced disease severity in the experimental mouse model. 

The researchers said targeting Cx43 channels with specific blockers such as INI-0602 could serve as a novel therapeutic strategy for MS. This, in turn, could facilitate the development of new treatments for patients with MS. Their findings also challenge a critical issue in MS treatment, that of limiting disease progression by targeting Cx43, where current treatments are found to be less effective.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, researchers plan to conduct clinical trials in the future to evaluate the safety and efficacy of INI-0602 in human patients with MS. Additionally, they also plan to look at the molecular mechanisms of Cx43 in influencing neuroinflammation and demyelination in detail.

The study was published in the journal Scientific Reports.