Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Theophylline induces remyelination and functional recovery in a mouse model of peripheral neuropathy
We previously published about this research in a story titled “Charcot-Marie-Tooth Disease: Theophylline Boosts Myelin Production in CMT1A Mice” which can be found here. The study was originally published in the scientific journal Biomedicines. You can read the full text of the study here.
What Happened?
Charcot-Marie-Tooth disease is a large group of related genetic disorders which primary impact the function of the peripheral nervous system. The mechanism of these diseases typically involves either a demyelinating or axonal degeneration effect. Charcot-Marie-Tooth disease type 1A involves a demyelinating mechanism and is the most frequently encountered type. As of now, there is no therapy or cure that can impede progression of the disease. In this study, researchers sought to understand if theophylline, a medication commonly used to treat respiratory illness, could have an effect on the demyelination in this disease.
Theophylline has diuretic, bronchial dilatation, smooth muscle relaxing, and CNS and cardiac stimulating properties. This study involved the use of a mouse model that imitated the mechanism of type 1A Charcot-Marie-Tooth disease. Ten model mice along with nine regular mice were involved in the study, with the regular mice being used as controls. The mice were between 24 and 29 days old and were treated with either saline or a 10mg/kg dose of theophylline for a period of four days.
21 days after the start of treatment, the mice underwent motor function testing. This testing was in the form of an inverted grid test. Mice were trained three times on the test, then were tested three times as well. In this test, the mouse grips onto the grid and moves along it while hanging upside down for thirty seconds or until it loses its grip. The study found that model mice treated with theophylline performed better than model mice that did not receive the treatment. They had more successful grabs, less missed steps, and took more steps overall; however, the time they stayed on the grid was similar to the non-treated mice, suggesting that while function improved, muscle strength itself had not.
The scientists also found that the treated mice showed remyelination in a percentage of their large-caliber axons when compared to untreated mice. However, the thickness of the myelin sheath of axons that retained myelin already was not affected. Overall, the findings suggest that theophylline could help remyelinate axons and improve motor function in Charcot-Marie-Tooth disease type 1A, as well as potentially in other peripheral neuropathies with a demyelination mechanism.
About Charcot-Marie-Tooth Disease
Charcot-Marie-Tooth disease is a hereditary disorder of the peripheral nervous system. It is most characterized by a progressive loss of touch sensation and muscle tissue in several different parts of the body. The cause of this disease is usually linked to a genetic mutation, but the mutation involved varies depending on the variant of Charcot-Marie-Tooth disease. There are multiple types of Charcot-Marie-Tooth disease, with all types aside from type 2 having a demyelination effect. Symptoms include foot drop, muscle wasting (typically in the arms, legs, and hands), painful muscle spasms, loss of sensation in the limbs, scoliosis, trouble speaking, chewing, and swallowing, and tremors. Treatment typically includes therapy and surgery in order to maintain function. There is no cure. The disease can occur early in life or as late as the 30s and 40s. To learn more about Charcot-Marie-Tooth disease, click here.
Why Does it Matter?
The findings from this research study could reveal a potential therapy for Charcot-Marie-Tooth disease type 1A and other demyelinating disorders. The results suggest that it could help maintain function for people that live with peripheral neuropathies of this type:
“This pilot study suggests that Theophylline treatment could be beneficial to promote myelination and thereby prevent axonal degeneration and enhance functional recovery in CMT1A patients.”
If theophylline is successful in human patients, it could lead to a significant breakthrough in the treatment of Charcot-Marie-Tooth disease. Further study, and eventually clinical trials, will be needed to understand the effect of theophylline more clearly:
“Hence, Theophylline should be further evaluated as a potential new therapeutic approach to sustainably treat demyelinating peripheral neuropathies such as CMT1A.”
While the development of such a treatment is still a ways off, that Charcot-Marie-Tooth disease community should take hope in the promising findings from this mouse model study.
