Beneficial Effect of Melatonin Alone or in Combination with Glatiramer Acetate and Interferon ß-1b on Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon ß-1b (IFNß-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNß-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNß-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS.

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

OBJECTIVES: Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. METHODS: Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. RESULTS: While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. CONCLUSIONS: While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

Benefit of endermology on indurations and panniculitis/lipoatrophy during relapsing-remitting multiple sclerosis long-term treatment with glatiramer acetate.

INTRODUCTION: Use of endermology (Endermologie®), which consists of a deep mechanical massage, in patients with multiple sclerosis receiving glatiramer acetate suggested improvements in injection-site indurations and panniculitis/lipoatrophy in our previous pilot experience. We aimed to assess the effect of endermology in a larger population of patients with multiple sclerosis receiving glatiramer acetate in clinical practice. METHODS: This was the extension phase of our pilot experience, carried out in patients with relapsing-remitting multiple sclerosis (RRMS) and indurations and/or panniculitis/lipoatrophy associated with long-term glatiramer acetate administration. Patients underwent endermology sessions twice per week, for 6 weeks, according to clinical practice. RESULTS: Seventy evaluable patients were included (mean age, 42.7±9.3 years; female, 95.7%; mean multiple sclerosis duration, 9.2±8.6 years; mean glatiramer acetate duration, 46.7±29.9 months). Fifty (71.4%) patients showed indurations and 58 (82.9%) panniculitis/lipoatrophy. After 12 endermology sessions, the number of patients with indurations significantly decreased (71.4% vs. 28.6%; p<0.001), as did the number of their indurations (4.2±3.6 vs. 3.7±3.4; p<0.001). Although the number of patients with panniculitis/lipoatrophy did not significantly decrease, there was a significant reduction in the number of areas of panniculitis/lipoatrophy (4.3±2.6 vs. 3.9±2.2; p<0.05). Forty-nine (98.0%) patients with indurations and 57 (98.3%) patients with panniculitis/lipoatrophy felt satisfied/very satisfied with treatment and considered endermology useful/very useful. Endermology was well tolerated, as some pain was reported in eight (11.4%) patients, discomfort in three (4.3%) patients, and local blotch/swelling and transient bruise in one (1.4%) patient each. Endermology enabled glatiramer acetate tolerance to be enhanced in 42 (60.0%) patients. CONCLUSION: This project represents the largest experience available supporting the benefit of endermology in the reduction/disappearance of indurations and improvement in panniculitis/lipoatrophy in patients with RRMS receiving long-term glatiramer acetate treatment. Moreover, these benefits also contributed to enhancing glatiramer acetate tolerance.