Dr. Charles Abrams, Professor of Neurology and Rehabilitation at the University of Illinois, Chicago, has discovered that inosine could potentially reduce nerve inflammation and offer moderate functional benefits in preclinical animal models of Charcot-Marie-Tooth disease type 1X.
How CMT1X Disrupts Nerve Function
CMT1X is the second most common form of CMT, caused by mutations in a gene called GJB1. This gene provides instructions for making a protein called Connexin 32, which is a gap junction protein in the Schwann cells of peripheral nerves. Gap junctions are channels that allow nutrients and signaling molecules to pass between cells. In CMT1X, these channels do not function properly, causing the disruption of Schwann cell activity and health, which leads to CMT disease.
Mice that lack the GJB1 gene provide a model of CMT1X and develop measurable neurodegenerative and behavioral features. Dr. Abrams has demonstrated that the nerves in CMT1X mice also have depleted amounts of systemic inosine, which is a naturally occurring molecule with anti-inflammatory properties.
Lack of Inosine Could Contribute to Inflammation
Dr. Abrams hypothesized that the lack of inosine in CMT1X contributes to inflammation in the peripheral nerves, which is thought to be a driver of the development and progression of CMT1X symptoms.
In this CMTRF-funded project, Dr. Abrams explored whether supplementation with inosine could improve disease symptoms in CMT1X mice. Positive results would suggest that inosine could serve as a potential treatment to improve CMT1X symptoms — an intriguing possibility, since inosine is a readily available supplement.
Dr. Abrams has demonstrated that he could effectively increase the levels of inosine in the nerves of CMT1X mice, leading to a significant reduction in nerve inflammation.
Additionally, there was evidence that some functional deficits, such as reduced grip strength and delayed muscle responses after nerve stimulation (prolonged distal latencies) improved with inosine treatment. It may be possible to enhance these effects by reducing clearance of inosine from the nerves or by utilizing longer treatment periods. Although these findings are encouraging, more studies are needed to be able to conclusively determine if inosine treatment provides any therapeutic benefit for CMT1X.
Next Steps in Research
Dr. Abrams plans to conduct additional studies to determine if the structure of the nerves in inosine-treated mice has improved. These findings will be critical for determining whether inosine treatment provides benefits directly to the peripheral nerves, or if the observed benefits are from indirect effects, which will be informative regarding future therapeutic testing efforts.
While inosine is widely available as a supplement, CMT Research Foundation advises those with CMT to seek advice from his/her treating physician before using it to determine its safety profile and any potential side effects. Your physician should also be familiar with any ongoing research regarding inosine that could better inform your decision of whether or not to use it.