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Considerable evidence demonstrated that the central role of reactive oxygen species and reactive nitrogen species (ROS and RNS) in the development of thermal hyperalgesia is associated to acute and chronic inflammation. Idebenone (IDE), a synthetic analogue of the endogenous cellular antioxidant coenzyme Q10 (CoQ10), is an active drug in the central nervous system which shows a protection in a variety of neurological disorders. Since it is lipophilic, poorly water soluble and highly bound to plasma proteins, different technological approaches have been explored to increase its solubility and new pharmaceutical properties. Therefore, it has been complexed with HP-β-cyclodextrins (HP) and its efficacy has been assessed in an animal model of carrageenan-induced thermal hyperalgesia. All male rats used for this study received a subplantar injection of carrageenan into the right hindpaw in the presence or absence of IDE alone and IDE/HP complex. We observed that IDE poorly reduced painful carrageenan effects whereas IDE/HP complex was able to prevent carrageenan-induced hyperalgesia and edema in a dose-dependent manner, reducing spinal MDA levels and protein nitration. Hence, our results demonstrated that when complexed with HP, idebenone exerts a potent analgesic and anti-inflammatory efficacy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10-18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated "by patient" (HR 0.33, p = 0.0187) and for "all BAEs" (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Friedreich ataxia is an inherited disorder characterized by degeneration of the peripheral and central nervous system and hypertrophic cardiomyopathy. Homozygous mutations in the frataxine (FXN) gene reduce expression of frataxin and cause accumulation of iron in the mitochondria. Deferiprone, an oral iron chelator, has been shown effective in cell and animal models of Friedreich ataxia. The results of a 6-month randomized, double blind placebo-controlled study suggested that deferiprone 20 mg/kg/day may reduce disease progression. The authors present their experience of 5 Friedreich ataxia patients treated with deferiprone (20 mg/kg/day), in addition to idebenone treatment, followed over a period of 10-24 months, under off-label authorization. The patients were monitored for laboratory parameters, cardiac assessment, neurological evaluations, and quality of life. The authors conclude that combined therapy of a low dose of deferiprone with idebenone is relatively safe, might improve neurological function, and seems to improve heart hypertrophy, warranting further studies., (© The Author(s) 2016.)

Idebenone is a synthetic analog of coenzyme Q; both share a quinone moiety but idebenone has a shorter lipophilic tail ending with a hydroxyl group. Differential scanning calorimetry experiments showed that both idebenone and idebenol widened and shifted the phase transition of 1,2-dipalmitoylphosphatidylcholine (DPPC) to a lower temperature and a phase separation with different concentrations of these molecules was observed. Also small angle X-ray diffraction and wide angle X-ray diffraction revealed that both, idebenone and idebenol, induced laterally separated phases in fluid membranes when included in DPPC membranes. Electronic profiles showed that both forms, idebenone and idebenol, reduced the thickness of the fluid membrane. (2)H NMR measurements showed that the order of the membrane decreased at all temperatures in the presence of idebenone or idebenol, the greatest disorder being observed in the segments of the acyl chains close to the lipid-water interface. (1)H NOESY MAS NMR spectra were obtained using 1-palmitoyl-2-oleoyl-phosphatidylcholine membranes and results pointed to a similar location in the membrane for both forms, with the benzoquinone or benzoquinol rings and their terminal hydroxyl group of the hydrophobic chain located near the lipid/water interface of the phospholipid bilayer and the terminal hydroxyl group of the hydrophobic chain of both compounds located at the lipid/water interface. Taken together, all these different locations might explain the different physiological behavior shown by the idebenone/idebenol compared with the ubiquinone-10/ubiquinol-10 pair in which both compounds are differently localized in the membrane., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Dominant optic atrophy (DOA) arises from mutations in the OPA1 gene that promotes fusion of the inner mitochondrial membrane and plays a role in maintaining ATP levels. Patients display optic disc pallor, retinal ganglion cell (RGC) loss and bilaterally reduced vision. We report a randomized, placebo-controlled trial of idebenone at 2000 mg/kg/day in 56 Opa1 mutant mice (B6;C3-Opa1(Q285STOP)), with RGC dendropathy and visual loss, and 63 wildtype mice. We assessed cellular responses in the retina, brain and liver and RGC morphology, by diolistic labeling, Sholl analysis and quantification of dendritic morphometric features. Vision was assessed by optokinetic responses. ATP levels were raised by 0.57 nmol/mg (97.73%, p=0.035) in brain from idebenone-treated Opa1 mutant mice, but in the liver there was an 80.35% (p=0.011) increase in oxidative damage. NQO1 expression in Opa1 mutant mice was reduced in the brain (to 30.5%, p=0.002) but not in retina, and neither expression level was induced by idebenone. ON-center RGCs failed to show major recovery, other than improvements in secondary dendritic length (by 53.89%, p=0.052) and dendritic territory (by 2.22 × 10(4) μm(2) or 90.24%, p=0.074). An improvement in optokinetic response was observed (by 12.2 ± 3.2s, p=0.003), but this effect was not sustained over time. OFF-center RGCs from idebenone-treated wildtype mice showed shrinkage in total dendritic length by 2.40 mm (48.05%, p=0.025) and a 47.37% diminished Sholl profile (p=0.029). Visual function in wildtype idebenone-treated mice was impaired (2.9 fewer head turns than placebo, p=0.007). Idebenone appears largely ineffective in protecting Opa1 heterozygous RGCs from dendropathy. The detrimental effect of idebenone in wildtype mice has not been previously observed and raises some concerns., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data., (Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.)

Thioredoxin 2 (TXN2; also known as Trx2) is a small mitochondrial redox protein essential for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Exome sequencing in a 16-year-old adolescent suffering from an infantile-onset neurodegenerative disorder with severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy, uncovered a homozygous stop mutation in TXN2. Analysis of patient-derived fibroblasts demonstrated absence of TXN2 protein, increased reactive oxygen species levels, impaired oxidative stress defence and oxidative phosphorylation dysfunction. Reconstitution of TXN2 expression restored all these parameters, indicating the causal role of TXN2 mutation in disease development. Supplementation with antioxidants effectively suppressed cellular reactive oxygen species production, improved cell viability and mitigated clinical symptoms during short-term follow-up. In conclusion, our report on a patient with TXN2 deficiency suggests an important role of reactive oxygen species homeostasis for human neuronal maintenance and energy metabolism., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Friedreich's ataxia (FRDA), a recessive neurodegenerative disorder commonly associated with hypertrophic cardiomyopathy, is caused by silencing of the frataxin (FXN) gene encoding the mitochondrial protein involved in iron-sulfur cluster biosynthesis., Methods: Application of our previously established FRDA human induced pluripotent stem cell (hiPSC) derived cardiomyocytes model as a platform to assess the efficacy of treatment with either the antioxidant coenzyme Q10 analog, idebenone (IDE) or the iron chelator, deferiprone (DFP), which are both under clinical trial., Results: DFP was able to more significantly suppress synthesis of reactive oxygen species (ROS) than IDE at the dosages of 25 μM and 10nM respectively which agreed with the reduced rate of intracellular accumulation of iron by DFP treatment from 25 to 50 μM. With regard to cardiac electrical-contraction (EC) coupling function, decay velocity of calcium handling kinetics in FRDA-hiPSC-cardiomyocytes was significantly improved by DFP treatment but not by IDE. Further mechanistic studies revealed that DFP also modulated iron induced mitochondrial stress as reflected by mitochondria network disorganization and decline level of respiratory chain protein, succinate dehydrogenase (CxII) and cytochrome c oxidase (COXIV). In addition, iron-response protein (IRP-1) regulatory loop was overridden by DFP as reflected by resumed level of ferritin (FTH) back to basal level and the attenuated transferrin receptor (TSFR) mRNA level suppression thereby reducing further iron uptake., Conclusions: DFP modulated iron homeostasis in FRDA-hiPSC-cardiomyocytes and effectively relieved stress-stimulation related to cardiomyopathy. The resuming of redox condition led to the significantly improved cardiac prime events, cardiac electrical-coupling during contraction., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Idebenone is a high permeable drug with very slight water solubility that affects the dissolution rate in the biological fluids, causing an irregular and limited in vivo absorption after oral administration. Moreover, it is marketed in Europe as tablets equivalent to 150 mg, with the consequent administration of multiple dose of solid unit to obtain the correct dose, a deterrent for the patients' compliance. According to these considerations, our goal was to develop spray-dried microparticles using a soluble β-cyclodextrin (CD) polymer and an enhancer of dissolution rate, such as carboxymethyl cellulose, to obtain a formulation easily dosable and soluble in water. The complex in solution was evaluated by phase solubility studies and the Idebenone/CD molar ratio selected was 1:1. According to Higuchi and Connors, adding carboxymethyl cellulose, a Bs-type profile was obtained. This result was due to the presence of carboxymethyl cellulose that competes with the CD in forming Idebenone microsystems, reducing of 10-fold the formulation bulk. UV-Vis absorption, (1)H nuclear magnetic resonance and circular dichroism showed the formation of the CD/Idebenone inclusion complex confirmed also by differential scanning calorimetry, Fourier transform infrared spectroscopy and fluorescence microscope (FM). The water solubility data and the in vitro dissolution tests performed in simulated gastric fluid, showed an increase of the drug water interaction due to the presence of the CD and carboxymethyl cellulose, both able to improve drug wettability, water solubility and dissolution rate. This approach seems to be suitable to produce microsystems which are able to enhance the in vivo absorption of Idebenone after oral administration and to increase the patient compliance.

Duchenne muscular dystrophy (DMD) is an X-linked myopathy resulting in progressive weakness and wasting of all the striated muscles including the respiratory muscles. The consequences are loss of ambulation before teen ages, cardiac involvement and breathing difficulties, the main cause of death. A cure for DMD is not currently available. In the last decades the survival of patients with DMD has improved because the natural history of the disease can be changed thanks to a more comprehensive therapeutic approach. This comprises interventions targeted to the manifestations and complications of the disease, particularly in the respiratory care. These include: 1) pharmacological intervention, namely corticosteroids and idebenone that significantly reduce the decline of spirometric parameters; 2) rehabilitative intervention, namely lung volume recruitment techniques that help prevent atelectasis and slows the rate of decline of pulmonary function; 3) scoliosis treatment, namely steroid therapy that is used to reduce muscle inflammation/degeneration and prolong ambulation in order to delay the onset of scoliosis, being an additional contribution to the restrictive lung pattern; 4) cough assisted devices that improve airway clearance thus reducing the risk of pulmonary infections; and 5) non-invasive mechanical ventilation that is essential to treat nocturnal hypoventilation, sleep disordered breathing, and ultimately respiratory failure. Without any intervention death occurs within the first 2 decades, however, thanks to this multidisciplinary therapeutic approach life expectancy of a newborn with DMD nowadays can be significantly prolonged up to his fourth decade. This review is aimed at providing state-of-the-art methods and techniques for the assessment and management of respiratory function in DMD patients.

The early stages of the atherosclerotic process are initiated by accumulation of oxidized low-density lipoprotein (oxLDL) and damage to the structure or function of the endothelium. Antioxidant supplementation may be a plausible strategy to prevent atherosclerotic disease by quenching excessive reactive oxidative species. In the present study, we demonstrated that idebenone at suitable concentrations significantly prevented oxLDL-induced endothelial dysfunction. The underlying mechanisms of idebenone included inhibition of oxidative damage, suppression of the down-regulation of Bcl-2 and up-regulation of Bax and cleaved caspase-3 in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL. Moreover, idebenone pretreatment inhibited oxLDL-mediated HUVECs damage by attenuating lipid peroxidation and promoting SOD activity. Finally, pro-incubation with idebenone inhibited mitochondrial dysfunction induced by oxLDL through the mitochondrial-dependent apoptotic pathway and GSK3β/β-catenin signalling pathways. In summary, idebenone is a promising agent in the treatment or prevention of atherosclerosis via inhibiting oxidative stress and improving mitochondrial function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Genetic defects in the UBE3A gene, which encodes for the imprinted E6-AP ubiquitin E3 ligase (UBE3A), is responsible for the occurrence of Angelman syndrome (AS), a neurodegenerative disorder which arises in 1 out of every 12,000-20,000 births. Classical symptoms of AS include delayed development, impaired speech, and epileptic seizures with characteristic electroencephalography (EEG) readings. We have previously reported impaired mitochondrial structure and reduced complex III in the hippocampus and cerebellum in the Ube3a(m-/p+) mice. CoQ10 supplementation restores the electron flow to the mitochondrial respiratory chain (MRC) to ultimately increase mitochondrial antioxidant capacity. A number of recent studies with CoQ10 analogues seem promising in providing therapeutic benefit to patients with a variety of disorders. CoQ10 therapy has been reported to be safe and relatively well-tolerated at doses as high as 3000mg/day in patients with disorders of CoQ10 biosynthesis and MRC disorders. Herein, we report administration of idebenone, a potent CoQ10 analogue, to the Ube3a(m-/p+) mouse model corrects motor coordination and anxiety levels, and also improves the expression of complexes III and IV in hippocampus CA1 and CA2 neurons and cerebellum in these Ube3a(m-/p+) mice. However, treatment with idebenone illustrated no beneficial effects in the reduction of oxidative stress. To our knowledge, this is the first study to suggest an improvement in mitochondrial respiratory chain dysfunction via bioenergetics modulation with a CoQ10 analogue. These findings may further elucidate possible cellular and molecular mechanism(s) and ultimately a clinical therapeutic approach/benefit for patients with Angelman syndrome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study investigates the effect of insulin combined with idebenone on blood-brain barrier (BBB) permeability in experimental streptozotocin-induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ-associated proteins occludin, and zonula occludens (ZO)-1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end-products (RAGE) and nuclear factor-κB (NF-κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin-5, and ZO-1 and that the ROS/AGE/RAGE/NF-κB signal pathway might be involved in the process., (© 2014 Wiley Periodicals, Inc.)

Idebenone (IDE) is a lipophilic benzoquinone electron carrier synthetic analogue of coenzyme Q10, which behaves as an antioxidant and free radical scavenging molecule. Recently, the therapeutic application of IDE in Leber's hereditary optic neuropathy has been discussed. This work was aimed at evaluating the encapsulation of IDE in solid-lipid nanoparticles (SLN). In particular, we tested the possibility of adapting the quasi-emulsion solvent diffusion technique, already proposed to produce polymeric nanoparticles, to prepare positively charged SLN with different compositions. Such a charge, due to the addition of a cationic lipid, would facilitate the interaction with the negatively charged eye surface epithelium, with a consequent longer pre-corneal residence time of the colloidal systems. In a preliminary evaluation of the produced IDE-loaded SLN, the antioxidant activity of the drug was demonstrated using an oxygen radical absorbance capacity assay. Encapsulation of the drug in the nanocarrier systems seems able to protect IDE from degradation and prolong its antioxidant potential.

Coenzyme Q10 is a ubiquitous component of cellular membranes and belongs to the class of benzoquinones that mainly differ with regards to the length and composition of their hydrophobic tail. The characteristic quinone group can accept electrons from various biological sources and is converted by a one electron transfer to the unstable semiquinone or by a two electron transfer to the more stable hydroquinone. This feature makes CoQ10 the bona fide cellular electron transfer molecule within the mitochondrial respiratory chain and also makes it a potent cellular antioxidant. These activities serve as justification for its popular use as food supplement. Another quinone with similarities to the naturally occurring CoQ10 is idebenone, which shares its quinone moiety with CoQ10, but at the same time differs from CoQ10 by the presence of a much shorter, less lipophilic tail. However, despite its similarity to CoQ10, idebenone cannot be isolated from any natural sources but instead was synthesized and selected as a pharmacologically active compound in the 1980s by Takeda Pharmaceuticals purely based on its pharmacological properties. Several recent clinical trials demonstrated some therapeutic efficacy of idebenone in different indications and as a consequence, many practitioners question if the freely available CoQ10 could not be used instead. Here, we describe the molecular and pharmacological features of both molecules that arise from their structural differences to answer the question if idebenone is merely a CoQ10 analogue as frequently perpetuated in the literature or a pharmaceutical drug with entirely different features., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

The article discusses about the allergic contact dermatitis caused by the idebenone found in an over-the-counter anti-ageing cream. According to the article, a caucasian woman had incurred skin rashes after applying an anti-ageing cream bought over-the-counter. It was said that she was treated with topical steroids to have the rashes treated.

The article discusses the occurrence of a newly described contact allergen in cosmetics, also an allergic contact dermatitis to hydroxydecyl ubiquinone. It is suggested that the chemical is from the quinone family promoted commercially as a synthetic analogue of Coenzyme Q-10. Also included is a case of a 50-year old woman who developed a facial rash after using Prevage.

In this study we prepared solid lipid nanoparticles (SLN), by the phase inversion temperature (PIT) method, using cetyl palmitate as solid lipid and three different non-ionic emulsifiers of the polyoxyethylene ethers family (ceteth-20, isoceteth-20, oleth-20). These SLN were loaded with different amount of idebenone (IDE), an antioxidant drug useful in the treatment of neurodegenerative diseases and skin oxidative damages. The differential scanning calorimetry (DSC) was employed to evaluate the effects of the different emulsifiers and the different amounts of drug loaded on the thermotropic behavior of SLN and to investigate how the drug was arranged into these nanoparticles. The IDE seemed to be located into different regions of the SLN depending on its concentration and on the surfactant used. The results of this study suggest that the calorimetric studies performed on SLN could provide valuable information to optimize SLN design and drug release from these carriers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Friedreich ataxia (FRDA) is an inherited, progressive, neurodegenerative disease for which there is presently no cure or effective therapeutic intervention. While physiologically complex, FRDA is caused by deficits in production and expression of frataxin (FXN), a mitochondrial protein important for regulation of iron-sulfur cluster containing enzymes in the cell. Depletion of FXN is associated with dysfunction of ATP synthesis, mitochondrial iron accumulation, potentially an increase in oxidative stress, and cellular dysfunction. Therapeutic development presently focuses on improving mitochondrial function and increasing FXN expression. Gene therapy, a field which has undergone significant advances in recent years, may offer a promising treatment for FRDA in the future. This collection of approaches provides many possible opportunities for treating this multisystem disorder.

Treatment of mitochondrial respiratory chain (MRC) disorders is extremely difficult, however, coenzyme Q10 (CoQ10) and its synthetic analogues are the only agents which have shown some therapeutic benefit to patients. CoQ10 serves as an electron carrier in the MRC as well as functioning as a potent lipid soluble antioxidant. CoQ10 supplementation is fundamental to the treatment of patients with primary defects in the CoQ10 biosynthetic pathway. The efficacy of CoQ10 and its analogues in the treatment of patients with MRC disorders not associated with a CoQ10 deficiency indicates their ability to restore electron flow in the MRC and/or increase mitochondrial antioxidant capacity may also be important contributory factors to their therapeutic potential., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: The objective of the study was to test the efficacy, safety and tolerability of triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia (FRDA) patients in a clinical pilot study., Patients and Methods: Patients included in this study were 10 males and three females, 14-61 years of age (average 30.2 ± 12.1), diagnosed with FRDA with normal ventricular function. Patients were treated with triple therapy with deferiprone at 5-25 mg/kg/day, idebenone at 10-20 mg/kg/day and riboflavin at 10-15 mg/kg/day for 15-45 months. The efficacy of this triple therapy was assessed by change from baseline on the scale for the assessment and rating of ataxia (SARA) and by the change from baseline in echocardiogram parameters., Results: Four patients discontinued due to adverse events (AEs) related with deferiprone. The annual worsening rate (AWR) was estimated in this series as 0.96 (CI 95%: 0.462-1.608) SARA score, whereas AWR for our FRDA cohort was estimated as 2.05 ± 1.23 SARA score. LVMI only decreased by 6.5 g/m(2) (6.2%) at the end of the first year of therapy. LVEF remained stable, except in case of three patients., Conclusion: Our results seem to indicate some uncertain benefit on the neurological and heart functions of this triple therapy in FRDA., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oxidative stress and mitochondrial dysfunction appear to contribute to neurodegenerative processes during multiple sclerosis (MS). Thus, antioxidants may represent a therapeutic option for MS. The antioxidant idebenone was proven to be beneficial in Friedreich's ataxia and Leber's hereditary optic neuropathy, two disorders caused by mitochondrial alterations. Here we showed that idebenone protected neuronal HT22 cells from glutamate-induced death in vitro. However, in experimental autoimmune encephalomyelitis, idebenone failed to affect disease incidence or onset when applied preventively, or to reduce disease severity when applied therapeutically. Histopathological examination of CNS from idebenone treated mice showed no improvement in inflammation, demyelination, or axonal damage. Thus, we hypothesize that idebenone treatment will likely not benefit patients with MS., (© 2013.)

In Duchenne muscular dystrophy (DMD) progressive weakness of respiratory muscles leads to a restrictive pulmonary syndrome that contributes to early morbidity and mortality. Currently no curative treatment exists for DMD. In a Phase II randomized placebo-controlled study (DELPHI) in 21 DMD boys at age 8-16 years, idebenone (450 mg/d) showed trends of efficacy for cardiac and respiratory endpoints. Since the DELPHI study population comprised both glucocorticoid-naïve subjects and glucocorticoid-users, we now report a post-hoc analysis investigating the effects of glucocorticoids and idebenone on markers of respiratory weakness, particularly peak expiratory flow (PEF) percent predicted (PEF%p). Baseline values of PEF%p correlated well with the percent predicted values for maximal inspiratory mouth pressure (MIP%p), forced vital capacity (FVC%p), and forced expired volume in 1 sec (FEV1%p). Baseline PEF%p and FVC%p were significantly higher in patients on concomitant glucocorticoids compared to glucocorticoid-naïve patients. In the latter subgroup, idebenone caused a 8.0 ± 12.1% improvement in PEF%p, whilst patients on placebo declined by -12.3 ± 17.9% (P < 0.05) in the course of the 12 month study. In patients receiving concomitant glucocorticoids, PEF%p remained stable (-0.4 ± 14.6%) in the idebenone group compared to a decline by -6.2 ± 12.4% (P = 0.24) in the placebo group. Idebenone showed a trend for efficacy on FVC%p only in glucocorticoid-naïve patients. Because of the study limitations, these data are exploratory and preclude any firm conclusions. In conclusion, PEF appears to be a sensitive respiratory function parameter that could be a valid and clinically relevant endpoint in intervention studies in DMD. In DELPHI the effect size of idebenone on PEF%p was significantly larger in steroid-naive patients, possibly indicating a maximum treatment effect reached by steroids or steroid-mediated suppression of idebenone's effects. The impact of standard care glucocorticoids on respiratory function will have to be considered in the planning of future interventional trials in DMD., (Copyright © 2012 Wiley Periodicals, Inc.)

Friedreich's ataxia is a debilitating progressive neurodegenerative disease associated with cardiomyopathy and other features. The underlying cause is a deficiency of the mitochondrial protein frataxin which causes mitochondrial iron deposition, increased oxidative stress and impaired adenosine triphosphate production. Over the last 15 years, multiple clinical trials have assessed the efficacy of antioxidant agents in this disease. This article reviews trials of the two most important agents, namely co-enzyme Q10 and idebenone., (© 2013 International Society for Neurochemistry.)

The present study aims to clarify the protective effect of supplementation with some antioxidants, such as idebenone (200 mg/kg, ip), melatonin (10 mg/kg, ip) and arginine (200 mg/kg, ip) and their combination, on liver function (T. protein, albumin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase), energetic parameters (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, inorganic phosphate, total adenylate, adenylate energy charge and potential phosphate). The effect on glycolytic and glycogenolytic enzymes (glucose, glycogen, glycogen phosphorylase, pyruvate kinase and phosphofructokinase against hypoxia) was also studied. The drugs were administered 24 and 1 h prior sodium nitrite intoxication. All biochemical parameters were estimated 1 h after sodium nitrite injection. Injection of sodium nitrite (75 mg/kg, sc) produced a significant disturbance in all biochemical parameters of liver function, energetic parameters and glycolytic and glycogenolytic enzymes. Hepatic damage was confirmed by histopathological examination of the liver as compared to controls. The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination, suggesting potential protection against sodium nitrite-induced hypoxia. It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.