Study suggests protein may be linked to myelin sheath restoration

August 25, 2020
A research team has identified an important mechanism that can be used to control the restoration of myelin sheaths following traumatic injury and in degenerative diseases such as multiple sclerosis. With the insights gained, the researchers were able to regenerate damaged myelin sheaths in mice by treating them with the active substance theophylline, thereby restoring their nerve cell function.

In the recent project, a research group at Johannes Gutenberg University Mainz and the University of Fribourg in Switzerland investigated how remyelination occurs in both peripheral and central nervous systems of mice. Theophylline promotes myelin reconstruction in both peripheral and central nervous systems. 

The neuroscientists identified a protein called eEF1A1 as a key factor in the process and found that eEF1A1 activated by acetylation prevents the remyelination process, but if eEF1A1 is deactivated by deacetylation, myelin sheaths can be rebuilt. The protein that deacetylates eEF1A1 is the enzyme called histone deacetylase 2 (HDAC2). Once they understood this process, they decided to try to control it by boosting the HDAC2 activity and its synthesis in cells. This was achieved by using the active substance theophylline, which is also present in tea leaves and has long been used in the treatment of asthma. 

In a mouse model, the use of theophylline during a period of four days resulted in significant recovery. Restoration of myelin sheaths was particularly impressive in the PNS, where they recovered completely. Regeneration also improved in the CNS, as there was rapid and efficient rebuilding of myelin sheaths in both young and old mice. A low dose of the active substance was sufficient to trigger the improvements – a big plus with regard to the known side-effects of theophylline, which occur at higher doses.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the study’s authors note the study shows that theophylline, by activating HDAC2, promotes eEF1A1 deacetylation, increases remyelination speed and efficiency after lesion of the PNS and CNS, and thus appears as a very promising compound to test in future studies to accelerate and promote remyelination after traumatic lesions or in the context of demyelinating disorders such as MS.

The findings were published in Nature Communications.

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