-arginine improves dystrophic phenotype in mice

Voisin, Vincent; Sebrié, Catherine; Matecki, Stéfan; Yu, Hua; Gillet, Brigitte; Ramonatxo, M; Israël, Maurice; Porte, Sabine de la

doi:10.1016/j.nbd.2005.02.010

Cited by 99 publications

(106 citation statements)

References 43 publications

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“…In particular, NO is generated by skeletal muscle to stimulate key actions in muscle repair, including activation of satellite cells and release of myotrophic factors (10)(11)(12). In addition, NO stimulates vasodilation, and thus increases the supply of oxygen and glucose uptake, and it triggers mitochondrial biogenesis, all of which contribute to preserve muscle from damage during contraction (13,14,25,26). Indeed, amelioration of the dystrophic phenotype had been observed in neuronal NO-synthase transgenic mice (15).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, amelioration of the dystrophic phenotype had been observed in neuronal NO-synthase transgenic mice (15). These studies stimulated investigations about the therapeutic potential of treatments based on administration of L-arginine, a metabolic precursor of NO, or molsidomine, a NO donor, to increase NO release (26,27). Although some amelioration of muscle morphology was observed, and in one study creatine kinase levels were reduced (26), those treatments did not yield recovery of muscle function, and they did not improve animal motility tests.…”

Section: Discussionmentioning

confidence: 99%

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Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy

Brunelli

Sciorati

D’Antona

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

148

160

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Duchenne muscular dystrophy is a relatively common disease that affects skeletal muscle, leading to progressive paralysis and death. There is currently no resolutive therapy. We have developed a treatment in which we combined the effects of nitric oxide with nonsteroidal antiinflammatory activity by using HCT 1026, a nitric oxide-releasing derivative of flurbiprofen. Here, we report the results of long-term (1-year) oral treatment with HCT 1026 of two murine models for limb girdle and Duchenne muscular dystrophies (␣-sarcoglycan-null and mdx mice). In both models, HCT 1026 significantly ameliorated the morphological, biochemical, and functional phenotype in the absence of secondary effects, efficiently slowing down disease progression. HCT 1026 acted by reducing inflammation, preventing muscle damage, and preserving the number and function of satellite cells. HCT 1026 was significantly more effective than the corticosteroid prednisolone, which was analyzed in parallel. As an additional beneficial effect, HCT 1026 enhanced the therapeutic efficacy of arterially delivered donor stem cells, by increasing 4-fold their ability to migrate and reconstitute muscle fibers. The therapeutic strategy we propose is not selective for a subset of mutations; it provides ground for immediate clinical experimentation with HCT 1026 alone, which is approved for use in humans; and it sets the stage for combined therapies with donor or autologous, genetically corrected stem cells.HCT 1026 ͉ satellite cells ͉ skeletal muscle ͉ ␣-sarcoglycan-null mice ͉ mdx mice

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy

Brunelli

Sciorati

D’Antona

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

148

160

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“…In several screened patients, there is evidence of deregulation of components involved in the ureacycle control, particularly the Arginase enzyme (12). L-arginine, the substrate for Arginase, has been successfully used in clinical pharmacotherapy where it significantly increases the utrophin level in dystrophic muscle (21) and improves cerebral ischemia in MELAS patients during the acute phase of stroke (22). These findings point to a possible role of amino acid metabolism in the pathogenesis of mitochondrial disease suggesting that: (i) the urea cycle may be crucial in disease progression, and (ii) steps in the arginine metabolic pathway are promising targets for novel therapeutic approaches.…”

Section: 'Metabolic Genes' Including Genes Involved In the Lipid Permentioning

confidence: 99%

Molecular research technologies in mitochondrial diseases: The microarray approach

Crimi

O’Hearn

Wallace

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

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SummaryMitochondria are ubiquitous in eukaryotic cells where they generate much of the cellular energy by the process of oxidative phosphorylation (OXPHOS). The approximately 1500 genes of the mitochondrial genome are distributed between the cytoplasmic, maternally-inherited, mitochondrial DNA (mtDNA) which encodes 37 genes and the nuclear DNA (nDNA) which encompasses the remaining mitochondrial genes. The interplay between the mtDNA and nDNA encoded mitochondrial genes and their role in mitochondrial disorders is still largely unclear. One approach for elucidating the pathophysiology of mitochondrial diseases has been to look at changes in the expression of mtDNA and nDNA-encoded genes in response to specific mitochondrial genetic defects. Initial studies of gene expression changes in response to mtDNA defect employed blot technologies to analyze changes in the expression of individual genes one at a time. While Southern/Northern blot experiments confirmed the importance of nDNA -mtDNA interactions in the pathophysiology of mitochondrial myopathy, the methodology used limited the number of genes that could be analyzed from each patient. This barrier has been overcome, in part by the advent of DNA microarray technology. In DNA microarrays gene sequences or oligonucleotides homologous to gene sequences are arrayed on a solid support. The RNA from the subject is then isolated, the mRNA converted to cDNA and the cDNA labeled with a fluorescent probe. The labeled cDNA is hybridized on the microarray and the fluorescence bound to each array is then quantified. Recently, these technologies have been applied to mitochondrial disease patient tissues and the presence of coordinate changes in mitochondrial gene expression confirmed. IUBMB Life, 57: 811-818, 2005

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“…55 In the mdx mouse, L-arginine supplementation was found to lead to less muscle necrosis, smaller amounts of collagen and fatty replacement without a change in the number of fibers with central nuclei, signifying the reduction of necrosis was not due to myofiber regeneration. 54 It has also been shown in this mouse model that L-arginine treated mdx muscle were less susceptible to contraction-induced injury. 56 Finally, a combination of creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid and betahydroxy-beta-methylbutyrate (HMB) improved strength and decreased fatigue in the mdx mouse.…”

Section: Supplementsmentioning

confidence: 70%

“…Nitric oxide synthetase (NOS) is found under the sarcolemma, as is utrophin, possibly implying a correlation between the expression of utrophin and activity of NOS. 54 In fact, when wild type and mdx mice were treated with nitric oxide donor or L-arginine, utrophin expression increased. 55 In the mdx mouse, L-arginine supplementation was found to lead to less muscle necrosis, smaller amounts of collagen and fatty replacement without a change in the number of fibers with central nuclei, signifying the reduction of necrosis was not due to myofiber regeneration.…”

Section: Supplementsmentioning

confidence: 99%

Therapeutics in Duchenne muscular dystrophy

Strober

2006

NeuroRX

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Summary: Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child's quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.

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-arginine improves dystrophic phenotype in mice

Cited by 99 publications

References 43 publications

Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy

Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy

Molecular research technologies in mitochondrial diseases: The microarray approach

Therapeutics in Duchenne muscular dystrophy

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