Melatonin Treatment Reduces Oxidative Damage and Normalizes Plasma Pro-Inflammatory Cytokines in Patients Suffering from Charcot-Marie-Tooth Neuropathy: A Pilot Study in Three Children

Abstract

Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic inflammation. Currently, there is no effective cure for CMT; herein, we investigated whether melatonin treatment may reduce the inflammatory and oxidative damage in CMT1A patients. Three patients, aged 8–10 years, were treated with melatonin (60 mg at 21:00 h plus 10 mg at 09:00 h), and plasma levels of lipid peroxidation (LPO), nitrites (NOx), IL-1β, IL-2, IL-6, TNF-α, INF-γ, oxidized to reduced glutathione (GSSG/GSH) ratio, and the activities of superoxide dismutase (SOD), glutathione-S transferase (GST), glutathione peroxidase (GPx), and reductase (GRd), were determined in erythrocytes at 3 and 6 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results showed increased activities of SOD, GST, GPx, and GRd in CMT1A patients, which were reduced at 3 and 6 months of treatment. The GSSG/GSH ratio significantly increased in the patients, returning to control values after melatonin treatment. The inflammatory process was confirmed by the elevation of all proinflammatory cytokines measured, which were also normalized by melatonin. LPO and NOx, which also were elevated in the patients, were normalized by melatonin. The results document beneficial effects of the use of melatonin in CMT1A patients to reduce the hyperoxidative and inflammatory condition, which may correlate with a reduction of the degenerative process.

Calcium Deregulation and Mitochondrial Bioenergetics in GDAP1-Related CMT Disease

“…These studies suggest that GDAP1 acts as a sensor of the reduced to oxidized glutathione ratio (GSH/GSSG) participating in the release of an antioxidative response causing the recovery of GSH/GSSG. These results suggest a possible role of oxidative stress and chronic inflammation in the pathogenesis of GDAP1-related CMT, as shown to occur in other forms of CMT such as CMT1A [30] or CMT1C [31].…”

Metabolic and Functional Improvements in a Patient with Charcot-Marie-Tooth Disease Type 2 after EGCG Administration: A Case Report

“…Moreover, said results would be in line with improvements obtained in CMT1A after administering another antioxidant and anti-inflammatory with mitochondrial benefits, such as melatonin. Particularly in this last study, improvements in oxidation state and inflammation levels [ 27 ] were observed after 3 months of treatment. IL-6 levels were also established within normal values, coinciding with our results after administering EGCG.…”

Aberrant NLRP3 Inflammasome Activation Ignites the Fire of Inflammation in Neuromuscular Diseases

“…In addition, these patients also suffer from acute, subacute or chronic inflammation along with oxidative stress (i.e., ROS) that is involved with progression of the disease [ 217 , 218 , 219 , 220 , 221 ]. Interestingly, melatonin treatment in CMT neuropathy patients reduces oxidative damage and normalizes plasma proinflammatory cytokines such as IL-1β [ 217 ]. This reduction in inflammasome activation may correlate with reduction of the degenerative process.…”