P4.01 ncRNAs originating from the dystrophin gene as biomarker for assessing antisense therapy (original) (raw)
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Beneficial effects of creatine supplementation in dystrophic patients
Muscle & Nerve, 2003
The effect of creatine (Cr) supplementation on muscle function and body composition of 12 boys with Duchenne muscular dystrophy and three with Becker dystrophy was evaluated by a randomized doubleblind cross-over study (3 g Cr or maltodextrin daily for 3 months, with wash-out period of 2 months). After placebo, no change was observed in maximal voluntary contraction (MVC) and resistance to fatigue, whereas total joint stiffness (TJS) was increased by ϳ25% (P Ͻ 0.05). The patients receiving Cr did not show any change in TJS, improved MVC by 15% (P ϭ 0.02), and almost doubled their resistance to fatigue (P Ͻ 0.001). In patients still independent of a wheelchair (n ϭ 5), bone mineral density increased by 3% (P Ͻ 0.05), and urinary excretion of collagen type I cross-linking Ntelopeptide declined to about one third (P Ͻ 0.001) after Cr. No adverse effect was observed. Thus, Cr may provide some symptomatic benefit in these patients.
Arthritis & Rheumatism, 2007
To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable. Methods. In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on 31 P magnetic resonance spectroscopy ( 31 P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids. Results. A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P ؍ 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P ؍ 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine. Conclusion. Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive.
The therapeutic potential of oral creatine supplementation in muscle disease
Medical Hypotheses, 1998
The decrease in intracellular creatine concentration observed in a number of muscle diseases may deplete energy homeostasis and may, therefore, be one of the factors determining and/or aggravating muscle weakness and degeneration. Two hypotheses are put forward in the present communication to explain: (i) the mechanisms leading to the disturbances in creatine metabolism found in various muscle diseases; and (ii) the potential of oral creatine supplementation in alleviating the clinical symptoms.
Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy
Neurology, 2004
Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of CrM (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and γ-glutamyl transferase activity and creatinine, urinary markers of myofibrillar protein breakdown (
Biomed Res Int, 2014
Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and 3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases.
Effect of creatine supplementation on skeletal muscle ofmdx mice
Muscle & Nerve, 2004
Dystrophic mice (mdx) and their controls (C57/Bl10) were fed for 1 month with a diet with or without creatine (Cr) enrichment. Cr supplementation reduced mass (by 19%, P Ͻ 0.01) and mean fiber surface (by 25%, P Ͻ 0.05) of fast-twitch mdx muscles. In both strains, tetanic tension increased slightly (9.2%) without reaching statistical significance (P ϭ 0.08), and relaxation time increased by 16% (P Ͻ 0.001). However, Cr had no protective effect on the other hallmarks of dystrophy such as: susceptibility to eccentric contractions; large numbers of centrally nucleated fibers in tibialis anterior; and elevated total calcium content, which increased by 85% (P ϭ 0.008) in gastrocnemius mdx muscles. In conclusion, Cr does not cure the disease although it may be a positive intervention for improvement of muscle function.
Amino Acids, 2012
Background and objectives. Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. Oral administration of creatine has been shown to improve muscle strength in healthy subjects. The objective of this study was to examine the effect of oral creatine supplementation on muscle weakness, disease activity and activities of daily living in patients with RA. Methods. During a period of 3 weeks, 12 patients with RA were treated with creatine monohydrate (20 g/day for 5 days followed by 2 g/day for 16 days). They were examined on entry and at the end of the study. The patients were investigated clinically, blood and urine samples were obtained, muscle biopsies were performed before and after treatment, muscle strength was determined, and self-administered patient questionnaires were completed. Results. From all patients we were able to obtain full clinical and questionnaire data, while biopsies were taken from 12 patients at the start and from nine patients at the end of the study. Muscle strength, as determined by the muscle strength index, increased in eight of 12 patients. In contrast, physical functional ability and disease activity did not change significantly. The creatine concentration in serum and skeletal muscle increased significantly, while creatine phosphate and total creatine did not increase in skeletal muscle. The skeletal muscle creatine content was associated with muscle strength at baseline but not after administration of creatine. The changes in muscle strength were not associated with the changes in skeletal muscle creatine or creatine phosphate. Conclusion. Although the skeletal muscle creatine content and muscle strength increased with creatine administration in some patients with RA, a clear clinical benefit could not be demonstrated for this treatment when the patients were considered as one group.
The Journal of Physiology, 2013
• Creatine (Cr) plays an important role in muscle energy homeostasis as a substrate in the creatine kinase phosphoryl exchange reaction, but the consequences of creatine depletion are incompletely understood. • We assessed the morphological, metabolic and functional consequences of systemic creatine depletion on skeletal muscle in a mouse model with deficiency of an essential enzyme in the biosynthesis of creatine (AGAT −/− mice). • We show that Cr depletion leads to several metabolic abnormalities in muscle, including reduced ATP, increased inorganic phosphate levels and reduced activities of proton-pumping respiratory chain enzymes and an elevated glycolytic contribution in ischaemic circumstances. • The Cr-depleted muscle suffers from reduced grip strength, severe atrophy and abnormal mitochondrial structures, increased overall mitochondrial content and an increased number of lipid droplets. • Oral Cr administration led to rapid accumulation in skeletal muscle (faster than in brain) and reversed all the muscle abnormalities, revealing that the condition of the AGAT −/− mice can be switched between Cr deficient and normal simply by dietary manipulation.