Improvement of Endurance of DMD Animal Model Using Natural Polyphenols

Abstract

Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, is characterized by muscular wasting caused by dystrophin deficiency that ultimately ends in force reduction and premature death. In addition to primary genetic defect, several mechanisms contribute to DMD pathogenesis. Recently, antioxidant supplementation was shown to be effective in the treatment of multiple diseases including muscular dystrophy. Different mechanisms were hypothesized such as reduced hydroxyl radicals, nuclear factor-κB deactivation, and NO protection from inactivation. Following these promising evidences, we investigated the effect of the administration of a mix of dietary natural polyphenols (ProAbe) on dystrophic mdx mice in terms of muscular architecture and functionality. We observed a reduction of muscle fibrosis deposition and myofiber necrosis together with an amelioration of vascularization. More importantly, the recovery of the morphological features of dystrophic muscle leads to an improvement of the endurance of treated dystrophic mice. Our data confirmed that ProAbe-based diet may represent a strategy to coadjuvate the treatment of DMD.

Fibrosis Rescue Improves Cardiac Function in Dystrophin-Deficient Mice and Duchenne Patient–Specific Cardiomyocytes by Immunoproteasome Modulation

“…Cardiac biopsy specimens were collected from ONX 0914etreated and untreated mdx mice, and the samples were prepared for analysis as previously described. 26 Mitochondrial respiratory chain enzymes and the citrate synthase activities were measured by means of a spectrophotometer as previously described. 27 The value of citrate synthase was used to normalize the values of the other complexes.…”

Preliminary Evidences of Safety and Efficacy of Flavonoids- and Omega 3-Based Compound for Muscular Dystrophies Treatment: A Randomized Double-Blind Placebo Controlled Pilot Clinical Trial

“…Advancing our understanding of the interactions between the immune system and dystrophic muscle has already led to identifying new potential immunosuppressant therapeutic strategies which will may not cure any of the muscular dystrophies but rather attenuate the severity of the disease (7, 53–58). Since nutrition is one of the major exogenous factors modulating different aspects of immune function, we recently tested the effects of natural polyphenols in dystrophin deficient animal model and demonstrated the amelioration of endurance and muscular inflammation and fibrosis (36). Following these promising evidences, we evaluated the safety and efficacy of a mix of natural polyphenols (FLAVOMEGA) in DMD, LGMD, and FSHD patients who were characterized for their muscle inflammatory background.…”

“…This treatment improved endurance and muscular features by reducing muscle fiber necrosis and fibrosis deposition and by increasing muscle mass. Although the mechanism of action is not completely clarified, we demonstrated its scavenger activity on ROS production and its anti-inflammatory properties regulating the recruitment of inflammatory cells in muscle tissues (36). In another work, we showed that mdx supplemented with specific branched-chain amino acid-enriched mixture (BCAAem) ameliorated the pathological phenotype (37).…”

“…In another work, we showed that mdx supplemented with specific branched-chain amino acid-enriched mixture (BCAAem) ameliorated the pathological phenotype (37). Here we report the results of a single center randomized double-blind placebo controlled study planned to validate our preclinical evidences (36) and assess the safety and partially the efficacy of dietary supplementation of flavonoids- and omega3-based natural supplement (hereafter referred to as FLAVOMEGA) in 29 dystrophic patients diagnosed for DMD, FSHD, and LGMD.…”

Supplementation with a selective amino acid formula ameliorates muscular dystrophy in mdx mice

“…Angiogenic factors, such as VEGF stimulate muscle regeneration in DMD 26 – 28 . Based on the benefits of pro-oxidative and angiogenic regulation in muscular dystrophy, we and other groups introduced the concept of dietary supplementation to ameliorate dystrophic muscle pathology 29 , 30 . Creatine, taurine, l -glutamine, and l -arginine have been shown to have limited benefits on muscle strength and dystrophic features, though these supplements remain to be formally evaluated in long-term studies 31 – 34 .…”