Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that treatment of mdx mouse muscular dystrophy with the glucocorticoid deflazacort prevents cardiomyopathic lesions and is accompanied by changes in metabolism and gene expression that reflect the improved tissue integrity. Cardiac muscle pathology, expression of alpha-cardiac myosin heavy chain, DNA synthesis, laminin, and basic fibroblast growth factor (bFGF) were examined to characterize dystrophy and changes with treatment. The potential of proton magnetic resonance spectroscopy (H-NMRS) to track cardiac dystrophy and deflazacort effects was also studied. Deflazacort (but not equipotent prednisone) reproducibly decreased lesion prevalence and severity. Treatment also produced cardiomyocyte hypertrophy and a 5.4-fold increase in alpha-cardiac myosin content. Expression of bFGF messenger RNA (mRNA), notable around lesions, rose 3.3-fold, and laminin expression rose 2.1-fold after deflazacort. Studies using H-NMRS showed a cardiac "signature" with less glycine and taurine than limb muscle or diaphragm and shifts with progression of dystrophy (distinct from normal aging) in many metabolites. Increased taurine, acetate, and succinate were present after 2 weeks of deflazacort treatment but were not present after 4 weeks. Although paired kinetic and functional studies of myocardium will be needed to determine the origin of such changes, these results demonstrate the potential application of H-NMRS to monitor clinical heart disease and treatment. In addition, the metabolic effects of deflazacort were substantial in preventing the progression of cardiomyopathy in mdx mice and included increased expression of protectant and stabilizing factors and hypertrophy of cardiac myocytes.
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PMID:Metabolic shifts and myocyte hypertrophy in deflazacort treatment of mdx mouse cardiomyopathy. 1118 Feb 2

Satellite cells, muscle precursor cells in skeletal muscle, are normally quiescent and become activated by disease or injury. A lack of dystrophin and changes in the expression or activity of neuronal nitric oxide synthase (NOS-I) affect the timing of activation in vivo. Nitric oxide synthase inhibition delays muscle repair in normal mice, and worsens muscular dystrophy in the mdx mouse, a genetic homologue of Duchenne muscular dystrophy. However, the potential role of activation and repair events mediated by nitric oxide in determining the outcome of steroid or other treatments for muscular dystrophy is not clear. We tested the hypothesis that the extent of repair in dystrophic muscles of mdx mice is partly dependent on NOS-Imu expression and activity. Myotube formation in regenerating muscle was promoted by deflazacort treatment of mdx dystrophic mice (P<0.05), and improved by combination with the nitric oxide synthase substrate, L-arginine, especially in the diaphragm. NOS-Imu mRNA expression and activity were present in satellite cells and very new myotubes of regenerating and dystrophic muscle. Deflazacort treatment resulted in increased NOS-Imu expression in regenerating muscles in a strong and specific correlation with myf5 expression (r=0.95, P<0.01), a marker for muscle repair. Nitric oxide synthase inhibition prevented the deflazacort-induced rise in NOS-Imu and myf5 expression in the diaphragm without affecting the diameter of non-regenerating fibres. These in vivo studies suggest that gains in NOS-Imu expression and nitric oxide synthase activity in satellite cells can increase the extent and speed of repair, even in the absence of dystrophin in muscle fibres. NOS-Imu may be a useful therapeutic target to augment the effects of steroidal or other treatments of muscular dystrophy.
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PMID:Correlated NOS-Imu and myf5 expression by satellite cells in mdx mouse muscle regeneration during NOS manipulation and deflazacort treatment. 1279 94

Although an increase in nitric oxide (NO) in muscle is reported to improve the outcome of deflazacort treatment for mdx mouse muscular dystrophy, the genetic homologue of Duchenne muscular dystrophy (DMD), the impact such treatment on the functional outcomes of the disease, including fiber susceptibility to exercise-induced injury, is not established. Experiments were designed to test whether treatment with deflazacort and L-arginine (a substrate for NO synthase, NOS) would change the extent of fiber injury induced by 24 h of voluntary exercise. The impact of exercise-related injury to induce a secondary regenerative response by muscle was also examined as corroborating evidence of muscle damage. Dystrophic mdx mice were treated for 3 wk with placebo, deflazacort, or deflazacort plus either L-arginine or N(G)-nitro-L-arginine methyl ester (a NOS inhibitor). Deflazacort, especially combined with L-arginine, spared quadriceps muscle from injury-induced regeneration (myf5 expression) compared with placebo treatment, despite an increase in membrane permeability immediately after exercise (assessed by Evans blue dye infiltration). Deflazacort alone prevented the typical progressive loss of function (measured as voluntary distance run over 24 h) that was observed 3 months later in placebo-treated mice. Therefore, combined deflazacort plus L-arginine treatment spared mdx dystrophic limb muscle from exercise-induced damage and the need for regeneration and induced a persistent functional improvement in distance run. Results suggest a potential new treatment option for improving the quality of life for boys with DMD.
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PMID:Persistent and improved functional gain in mdx dystrophic mice after treatment with L-arginine and deflazacort. 1646 57

Conventional oral steroids like prednisolone have various adverse effects both during short-term and long-term use. Hence a search for an alternative oral steroid with fewer side-effects is underway throughout the world. Deflazacort, an oxazoline derivative, is a step in this direction. The number of large randomized trials using deflazacort for steroid-responsive disorders in children is limited. Use of deflazacort has been explored largely in patients with Duchenne's muscular dystrophy. Preliminary data suggest reduced osteoporosis, lesser growth retardation and weight gain with use of deflazacort, as compared to other steriods. In view of the limited data demonstrating superiority of deflazacort over the available oral steroids and its prohibitive cost, it is early to advocate widespread use of this drug in children.
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PMID:Deflazacort. 2008 85