Theophylline Produces Accelerated Remyelination in the Central Nervous System of Mice

The myelin sheathing around axons is necessary for the proper function of nervous system tissue. Demyelinating conditions such as multiple sclerosis, an autoimmune disease in which the immune system attacks myelin, well illustrate the severe consequences that result from a sizable loss of myelin. Unfortunately, the integrity of myelin sheathing declines with age for everyone, most likely the result of disruption and damage in the oligodendrocyte cell population responsible for maintaining these structures. Evidence suggests that this contributes to cognitive decline and other issues. Thus it is worth keeping an eye on progress towards therapies that might enhance the generation and repair of myelin sheathing. The work noted here is an example of the type, in which the drug theophylline is shown to improve recovery from myelin loss in mice.

Neurons are composed of axons, i.e., long fiber-like extensions that transmit signals to other cells. Many of them are surrounded by a myelin sheath, a thick fatty layer that protects them and helps to transfer stimuli rapidly. Without myelin, the functional capacity of neurons - and therefore of the whole nervous system - is limited and neurons can easily degenerate. Multiple sclerosis (MS) is one of the diseases associated with myelin sheath degradation. MS patients suffer successive episodes of demyelination resulting in a progressive loss of function of their nervous system. Remyelination of the axons can prevent this.

Intact myelin sheaths are a prerequisite for the healthy functioning of the peripheral and central nervous systems. If the peripheral nervous system (PNS) is damaged, in an accident involving injury to the arms or legs for example, the axons and their myelin sheaths can recover relatively well. However, the central nervous system (CNS) is completely different in this regard as there is no efficient restoration of the axons and therefore of the myelin sheath after a lesion. This means that CNS injuries usually result in permanent paralysis - as in the case of MS when loss of myelin leads to axon degeneration. Further, the capacity of the body to remyelinate decreases dramatically with age.

Researchers recently investigated how remyelination occurs in both peripheral and central nervous systems of mice. 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).

The researchers decided to try to control this process by boosting HDAC2 activity and its synthesis in cells. This was achieved by using the active substance theophylline, which has long been used in the treatment of asthma. In a mouse model, the use of theophylline over 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.

Link: https://www.uni-mainz.de/presse/aktuell/11912_ENG_HTML.php

Comments

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https://www.sciencedaily.com/releases/2020/08/200817191737.htm

'In vitro, the addition of the compound to rat cells most responsible for myelination -- oligodendrocyte precursor cells, or OPCs -- spurred induction of IL-33 and rapidly increased the expression of myelin genes and proteins, including dose-dependent increases in myelin basic protein;

In two animal models of demyelination, treatment with the compound increased the relative presence of IL-33-expressing OPCs and led to reduced paralysis;

In an animal model of demyelination treated with the compound, dissection and electron microscopy showed dose-dependent increases in myelination.'

Posted by: Jones at September 1st, 2020 1:39 PM

Our dog has Degenerative Myelopthy. We want to try theophylline to help her restore her myelin sheath. Can you tell me what dose we should try? She is a 62 lb. Boxer. We have a friend with MS also, and we've told her about the study. She would like to know more too.
thank you,

Jeff

Posted by: Jeffrey Stevens at December 30th, 2020 4:46 PM

I have had MS30 yrs with a EDSS rating of 7[can't stand/walk], about near bedridden as I want to get. recently [6months agowent to Mexico for a HSCT [stem cell transplant] which by harvesting my stem cells,then killing my ms compromised immune system with chemo,then reintroducing my stem cells back into my body to regrow a new immune system free of ms. It seems to have been sucessful, so now to regrow mylin to close up my lesion covered brain/spinal colume. the mice were injected with low dose theophylline over 4 days. Will taking an oral dose achieve the same thing starting off at 6oomg twice a day? I realize the OD potential with the adverse side effects of this drug, but this is my last kick of the can [do or die] so I am blindly jumping off the cliff hoping the best.due to liability no one will comment.Does anyone have ahy positive advice or suggestions to aid me in proper dosages or relative criteria.doing nothing is not an option,reguardless of outcome.

Posted by: JD Phillips at December 9th, 2021 3:01 PM

I wrote the above paragraph wondering about a doseage of theophylline to try to stimulate the regrowth of remylation??I am currently trying a self med protocal but think I surpassed the optimum doseage [sweet spot] a t 300 mg daily - any opinions out there ?? Big pharma is working on a syncetic version of theopolline so they can patent it and reap the profits for their troubles, but that is a few yrs out yet, which I don't have.

Posted by: JD Phillips at February 20th, 2022 4:16 PM

Theophylline seem to have a rather strange influence on my damaged spinal cord.
I had transverse myelitis 2 years ago and it left me with few "scars". The only time I feel these scars is when I exercise (more vibrations, more severe symptoms) and actually always after drinking green tea. After reading several papers on Theophylline, could it be that it is actually healing even though the symptoms are coming back?
Before TM, I drank gallons of green tea every day and after my hospitalization, I stopped to be sure.
So now I have no idea if my immune system hates green tea and is trying to cripple me again or if it is this Remyelination.
Thoughs?

Posted by: Jakub L at January 23rd, 2023 6:32 PM
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