Astroglia, a class of neural cellsoverproduce, in MS patients, a channel protein known as connexin 43. This overproduction facilitates the release of pro-inflammatory chemicals that trigger a harmful immune response, ultimately causing damage to neurons, characteristic of MS.
Connexin 43 (Cx43) is a protein involved in cellular communication
-but also cardiac function-.
well that MS affects more than 3 million people worldwidelike most neurodegenerative diseases, its treatment options are very limited. So does understanding the disease, although it is well established that MS is caused by the patient’s immune system attacking their central nervous system. Specifically, the immune system attacks the protective myelin sheath that surrounds nerve fibers in the brain and spinal cord, causing demyelination and damage.
Previous research by the same team (2013) had already shown that Cx43 production was increased in support cells called astroglia, close to chronic MS lesions. While Cx43 is essential for intercellular signaling and plays a key role in modulating the immune system, researchers then hypothesized that the protein could play an essential role in promoting neuroinflammation which, in the context of MS, ultimately leads to demyelination.
The studycarried out on an animal model of MS supports this hypothesis and confirms that blocking the protein using an inhibitor (INI-0602) indeed reduces the symptoms of MS and identifies connexin 43 as a new therapeutic target for MS.
- INI-0602 effectively “mouths” and blocks Cx43 channels, reducing MS symptoms – in mice;
- INI-0602 not only suppresses the overproduction of Cx43 in astroglia, but also alleviates many features of MS, including demyelination and excessive infiltration of immune cells into the nervous system;
- INI-0602 reduces the levels of pro-inflammatory cytokines (proteins produced by immune cells that trigger the immune system) and increases those of anti-inflammatory cytokines in the cerebrospinal fluid;
- INI-0602 alters calcium signaling in astroglial cells, limiting their ability to promote inflammation.
Together, these effects reduce disease severity in the animal model of MS.
The implications are important, with the prospect of future therapies against MS. “Targeting Cx43 channels with specific blockers like INI-0602 appears to be a promising strategy.”
And, probably also, against other neurodegenerative diseases where activation of astroglia and channels like Cx43 are disease-modifying factors, such as amyotrophic lateral sclerosis.
