Researchers identify a new gene to treat multiple sclerosis

Multiple sclerosis, or MS, is a disease that affects the central nervous system and can eventually lead to muscle tremors and thus loss of balance.

Researchers identify a new gene to treat multiple sclerosis
Karl Carlström. Image Credit: Stefan Zimmerman.

Now, Karolinska Institute scientists have found a gene—called Gsta4—that safeguards a specific kind of cell in the brain from being damaged. It is believed that the study results could help enhance the treatment of this serious disorder. The study has been published in the Nature Communications journal.

Taken together, our findings are particularly interesting for several reasons. Too little is known about the mechanisms behind progressive MS, by which I mean the phase of the disease in which oligodendrocytes and neurons in the brain die without re-forming.”

Karl Carlström, Study Corresponding Author and Researcher, Department of Clinical Neuroscience, Karolinska Institute

Neurons in the brain can be compared to electric wires, whose insulating and protective sheaths are crucial for their functions. The cells providing such insulation are known as oligodendrocytes. The immune system specifically attacks these cells in an early stage of MS.

Karolinska Institute researchers have analyzed potential mechanisms that influence the optimal maturation of the oligodendrocytes into functional cells as well as their survival at the time of this process.

MS is known to be a disease of the central nervous system—that is, the brain and spinal cord—and can persist for several years, leading to walking difficulties, loss of sensation, mood swings, visual impairment, and tremors, among other problems, in a majority of the cases.

Efficacious drugs

During the early stage of MS, the oligodendrocytes are capable of reforming and maturing into fresh insulating cells, thereby restoring the function of neurons in the patient. But this function is slowly inhibited and so does the ability of the insulating and protective cells to mature completely. Since investigators are unaware of the mechanism behind this, no treatment is available as yet.

In our study we identify a gene called Gsta4, which is especially important to the maturation process of oligodendrocytes. Interestingly, it seems some known and future MS drugs speed up this process in rats through this very gene. Remove Gsta4 and they lose this effect.”

Karl Carlström, Study Corresponding Author and Researcher, Department of Clinical Neuroscience, Karolinska Institute

Through rat experiments, the team was able to demonstrate that oligodendrocytes containing high concentrations of the Gsta4 gene mature more rapidly and are relatively more tenable when compared to those with normal gene levels. This implies that damage that occurs in the form of compromised insulation around the neurons can be repaired more rapidly.

Prevents cell-death

The team believes that the gene performs this repairing process by preventing death (apoptotic) signaling in the oligodendrocytes. Such signals can be activated by an array of factors and also involve the power plants, or mitochondria, of the cells; mitochondria appear to be protected by high levels of the Gsta4 gene.

The team was ultimately able to demonstrate that at high levels of Gsta4, recovery takes place more rapidly in an experimental MS model when compared to animals that have normal levels of the gene. The research demonstrates that during the growth and maturity of cells, the mitochondria should be protected and the apoptotic signals should be restricted.

The findings can offer a deeper insight into the MS disease and the mechanism of action of the medications in use, or to be used soon, for this disorder.

Source:
Journal reference:

Carlström, K. E., et al. (2020). Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis. Nature Communications. doi.org/10.1038/s41467-020-17871-5.

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