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Reviews

Emerging drugs for Duchenne muscular dystrophy

, PhD, , PhD & , MD
Pages 261-277 | Published online: 25 May 2012

Bibliography

  • Center for Disease Control and Prevention (CDC). Prevalence of Duchenne/Becker muscular dystrophy among males aged 5-24 years - four states, 2007. MMWR Morb Mortal Wkly Rep 2009;58:1119-22
  • Mendell JR, Shilling C, Leslie ND, Evidence-based path to newborn screening for duchenne muscular dystrophy. Ann Neurol 2012;71:304-13
  • Brooke MH, Fenichel GM, Griggs RC, Clinical investigation in duchenne dystrophy: 2. Determination of the “power” of therapeutic trials based on the natural history. Muscle Nerve 1983;6:91-103
  • Eagle M, Baudouin SV, Chandler C, Survival in duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord 2002;12:926-9
  • England SB, Nicholson LV, Johnson MA, Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 1990;343:180-2
  • Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol 2003;2:731-40
  • Koenig M, Hoffman EP, Bertelson CJ, Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987;50:509-17
  • Bonilla E, Samitt CE, Miranda AF, Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 1988;54:447-52
  • Oudet C, Hanauer A, Clemens P, Two hot spots of recombination in the DMD gene correlate with the deletion prone regions. Hum Mol Genet 1992;1:599-603
  • Chamberlain JS, Gibbs RA, Ranier JE, Deletion screening of the duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 1988;16:11141-56
  • Beggs AH, Koenig M, Boyce FM, Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 1990;86:45-8
  • Lalic T, Vossen RH, Coffa J, Deletion and duplication screening in the DMD gene using MLPA. Eur J Hum Genet 2005;13:1231-4
  • Dent KM, Dunn DM, von Niederhausern AC, Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A 2005;134:295-8
  • Flanigan KM, von Niederhausern A, Dunn DM, Rapid direct sequence analysis of the dystrophin gene. Am J Hum Genet 2003;72:931-9
  • Zebracki K, Drotar D. Pain and activity limitations in children with duchenne or becker muscular dystrophy. Dev Med Child Neurol 2008;50:546-52
  • Chen JY, Clark MJ. Family function in families of children with duchenne muscular dystrophy. Fam Community Health 2007;30:296-304
  • Mendell JR, Vaughn AJ. Duchenne muscular dystrophy: ethical and emotional considerations in long-term management. Semin Neurol 1984;4:98-103
  • Mendell JR, Moxley RT, Griggs RC, Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N Engl J Med 1989;320:1592-7
  • Biggar WD, Harris VA, Eliasoph L, Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord 2006;16:249-55
  • Griggs RC, Moxley RT III, Mendell JR, Prednisone in duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. Arch Neurol 1991;48:383-8
  • Griggs RC, Moxley RT III, Mendell JR, Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology 1993;43:520-7
  • Escolar DM, Hache LP, Clemens PR, Randomized, blinded trial of weekend vs daily prednisone in duchenne muscular dystrophy. Neurology 2011;77:444-52
  • Balaban B, Matthews DJ, Clayton GH, Corticosteroid treatment and functional improvement in duchenne muscular dystrophy: long-term effect. Am J Phys Med Rehabil 2005;84:843-50
  • King WM, Ruttencutter R, Nagaraja HN, Orthopedic outcomes of long-term daily corticosteroid treatment in duchenne muscular dystrophy. Neurology 2007;68:1607-13
  • van Deutekom JC, Janson AA, Ginjaar IB, Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med 2007;357:2677-86
  • Kinali M, Arechavala-Gomeza V, Feng L, Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol 2009;8:918-28
  • Davies J, Gilbert W, Gorini L. Streptomycin, suppression, and the code. Proc Natl Acad Sci USA 1964;51:883-90
  • Anderson WF, Gorini L, Breckenridge L. Role of ribosomes in streptomycin-activated suppression. Proc Natl Acad Sci USA 1965;54:1076-83
  • Squire S, Raymackers JM, Vandebrouck C, Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system. Hum Mol Genet 2002;11:3333-44
  • Nethery D, Callahan LA, Stofan D, PLA(2) dependence of diaphragm mitochondrial formation of reactive oxygen species. J Appl Physiol 2000;89:72-80
  • Acharyya S, Villalta SA, Bakkar N, Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in duchenne muscular dystrophy. J Clin Invest 2007;117:889-901
  • Haidet AM, Rizo L, Handy C, Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Proc Natl Acad Sci USA 2008;105:4318-22
  • Rodino-Klapac LR, Haidet AM, Kota J, Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve 2009;39:283-96
  • Sander M, Chavoshan B, Harris SA, Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Proc Natl Acad Sci USA 2000;97:13818-23
  • Desguerre I, Mayer M, Leturcq F, Endomysial fibrosis in duchenne muscular dystrophy: a marker of poor outcome associated with macrophage alternative activation. J Neuropathol Exp Neurol 2009;68:762-73
  • Mendell JR, Campbell K, Rodino-Klapac L, Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med 2010;363:1429-37
  • Meng J, Muntoni F, Morgan JE. Stem cells to treat muscular dystrophies - where are we? Neuromuscul Disord 2011;21:4-12
  • Winnard AV, Mendell JR, Prior TW, Frameshift deletions of exons 3 – 7 and revertant fibers in duchenne muscular dystrophy: mechanisms of dystrophin production. Am J Hum Genet 1995;56:158-66
  • Burrow KL, Coovert DD, Klein CJ, Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group. Neurology 1991;41:661-6
  • McClorey G, Fletcher S, Wilton S. Splicing intervention for duchenne muscular dystrophy. Curr Opin Pharmacol 2005;5:529-34
  • Malik V, Rodino-Klapac LR, Viollet L, Gentamicin-induced readthrough of stop codons in duchenne muscular dystrophy. Ann Neurol 2010;67:771-80
  • Hirawat S, Welch EM, Elfring GL, Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol 2007;47:430-44
  • Mann CJ, Honeyman K, Cheng AJ, Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse. Proc Natl Acad Sci USA 2001;98:42-7
  • Goyenvalle A, Babbs A, Powell D, Prevention of dystrophic pathology in severely affected dystrophin/utrophin-deficient mice by morpholino-oligomer-mediated exon-skipping. Mol Ther 2010;18:198-205
  • Yokota T, Lu QL, Partridge T, Efficacy of systemic morpholino exon-skipping in duchenne dystrophy dogs. Ann Neurol 2009;65:667-76
  • Goemans NM, Tulinius M, van den Akker JT, Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med 2011;364:1513-22
  • Cirak S, Arechavala-Gomeza V, Guglieri M, Exon skipping and dystrophin restoration in patients with duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 2011;378:595-605
  • Barton-Davis ER, Cordier L, Shoturma DI, Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J Clin Invest 1999;104:375-81
  • Wagner KR, Hamed S, Hadley DW, Gentamicin treatment of duchenne and becker muscular dystrophy due to nonsense mutations. Ann Neurol 2001;49:706-11
  • Politano L, Nigro G, Nigro V, Gentamicin administration in duchenne patients with premature stop codon. Preliminary results. Acta Myol 2003;22:15-21
  • Welch EM, Barton ER, Zhuo J, PTC124 targets genetic disorders caused by nonsense mutations. Nature 2007;447:87-91
  • Clinical Trials. Available from: http://www.clinicaltrials.gov/ct2/results?term=ptc124
  • Rowe SM, Clancy JP. Pharmaceuticals targeting nonsense mutations in genetic diseases: progress in development. BioDrugs 2009;23:165-74
  • Wilschanski M, Miller LL, Shoseyov D, Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis. Eur Respir J 2011;38:59-69
  • Tinsley J, Deconinck N, Fisher R, Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat Med 1998;4:1441-4
  • Gilbert R, Nalbantoglu J, Petrof BJ, Adenovirus-mediated utrophin gene transfer mitigates the dystrophic phenotype of mdx mouse muscles. Hum Gene Ther 1999;10:1299-310
  • Tinsley JM, Fairclough RJ, Storer R, Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS One 2011;6:e19189
  • Moorwood C, Lozynska O, Suri N, Drug discovery for duchenne muscular dystrophy via utrophin promoter activation screening. PLoS ONE 2011;6:e26169
  • Krag TO, Bogdanovich S, Jensen CJ, Heregulin ameliorates the dystrophic phenotype in mdx mice. Proc Natl Acad Sci USA 2004;101:13856-60
  • Amenta AR, Yilmaz A, Bogdanovich S, Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice. Proc Natl Acad Sci USA 2011;108:762-7
  • McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997;387:83-90
  • Schuelke M, Wagner KR, Stolz LE, Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 2004;350:2682-8
  • Wagner KR, Fleckenstein JL, Amato AA, A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol 2008;63:561-71
  • Bogdanovich S, Krag TO, Barton ER, Functional improvement of dystrophic muscle by myostatin blockade. Nature 2002;420:418-21
  • Cadena SM, Tomkinson KN, Monnell TE, Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type. J Appl Physiol 2010;109:635-42
  • Lee SJ, Lee YS, Zimmers TA, Regulation of muscle mass by follistatin and activins. Mol Endocrinol 2010;24:1998-2008
  • Amthor H, Macharia R, Navarrete R, Lack of myostatin results in excessive muscle growth but impaired force generation. Proc Natl Acad Sci USA 2007;104:1835-40
  • Fryburg DA. Insulin-like growth factor I exerts growth hormone- and insulin-like actions on human muscle protein metabolism. Am J Physiol 1994;267:E331-6
  • Barton ER, Morris L, Musaro A, Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. J Cell Biol 2002;157:137-48
  • Shavlakadze T, White J, Hoh JF, Targeted expression of insulin-like growth factor-I reduces early myofiber necrosis in dystrophic mdx mice. Mol Ther 2004;10:829-43
  • Lynch GS, Cuffe SA, Plant DR, IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice. Neuromuscul Disord 2001;11:260-8
  • Gregorevic P, Plant DR, Leeding KS, Improved contractile function of the mdx dystrophic mouse diaphragm muscle after insulin-like growth factor-I administration. Am J Pathol 2002;161:2263-72
  • Bernasconi P, Torchiana E, Confalonieri P, Expression of transforming growth factor-beta 1 in dystrophic patient muscles correlates with fibrosis. Pathogenetic role of a fibrogenic cytokine. J Clin Invest 1995;96:1137-44
  • Sun G, Haginoya K, Wu Y, Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy. J Neurol Sci 2008;267:48-56
  • Gosselin LE, Williams JE, Deering M, Localization and early time course of TGF-beta 1 mRNA expression in dystrophic muscle. Muscle Nerve 2004;30:645-53
  • Passerini L, Bernasconi P, Baggi F, Fibrogenic cytokines and extent of fibrosis in muscle of dogs with X-linked golden retriever muscular dystrophy. Neuromuscul Disord 2002;12:828-35
  • Cohn RD, van Erp C, Habashi JP, Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states. Nat Med 2007;13:204-10
  • Spurney CF, Sali A, Guerron AD, Losartan decreases cardiac muscle fibrosis and improves cardiac function in dystrophin-deficient mdx mice. J Cardiovasc Pharmacol Ther 2011;16:87-95
  • Bish LT, Yarchoan M, Sleeper MM, Chronic losartan administration reduces mortality and preserves cardiac but not skeletal muscle function in dystrophic mice. PLoS One 2011;6:e20856
  • McGaha TL, Phelps RG, Spiera H, Halofuginone, an inhibitor of type-I collagen synthesis and skin sclerosis, blocks transforming-growth-factor-beta-mediated Smad3 activation in fibroblasts. J Invest Dermatol 2002;118:461-70
  • Nagler A, Firman N, Feferman R, Reduction in pulmonary fibrosis in vivo by halofuginone. Am J Respir Crit Care Med 1996;154:1082-6
  • Huebner KD, Jassal DS, Halevy O, Functional resolution of fibrosis in mdx mouse dystrophic heart and skeletal muscle by halofuginone. Am J Physiol Heart Circ Physiol 2008;294:H1550-61
  • Turgeman T, Hagai Y, Huebner K, Prevention of muscle fibrosis and improvement in muscle performance in the mdx mouse by halofuginone. Neuromuscul Disord 2008;18:857-68
  • Carter NJ. Pirfenidone: in idiopathic pulmonary fibrosis. Drugs 2011;71:1721-32
  • Gosselin LE, Williams JE, Personius K, A comparison of factors associated with collagen metabolism in different skeletal muscles from dystrophic (mdx) mice: impact of pirfenidone. Muscle Nerve 2007;35:208-16
  • Taniguti AP, Pertille A, Matsumura CY, Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF-beta1 blocker. Muscle Nerve 2011;43:82-7
  • Bizario JC, Cerri DG, Rodrigues LC, Imatinib mesylate ameliorates the dystrophic phenotype in exercised mdx mice. J Neuroimmunol 2009;212:93-101
  • Huang P, Zhao XS, Fields M, Imatinib attenuates skeletal muscle dystrophy in mdx mice. FASEB J 2009;23:2539-48
  • Eisenberg I, Eran A, Nishino I, Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci USA 2007;104:17016-21
  • Cacchiarelli D, Martone J, Girardi E, MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway. Cell Metab 2010;12:341-51
  • Hauser E, Hoger H, Bittner R, Oxyradical damage and mitochondrial enzyme activities in the mdx mouse. Neuropediatrics 1995;26:260-2
  • Whitehead NP, Yeung EW, Froehner SC, Skeletal muscle NADPH oxidase is increased and triggers stretch-induced damage in the mdx mouse. PLoS ONE 2010;5:e15354
  • Tidball JG, Wehling-Henricks M. The role of free radicals in the pathophysiology of muscular dystrophy. J Appl Physiol 2007;102:1677-86
  • Messina S, Bitto A, Aguennouz M, Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances muscle function in Mdx mice. Exp Neurol 2006;198:234-41
  • Whitehead NP, Pham C, Gervasio OL, N-Acetylcysteine ameliorates skeletal muscle pathophysiology in mdx mice. J Physiol 2008;586:2003-14
  • Nakae Y, Hirasaka K, Goto J, Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice: a quantitative histological, immunohistochemical and electrophysiological study. Histochem Cell Biol 2008;129:489-501
  • Dorchies OM, Wagner S, Vuadens O, Green tea extract and its major polyphenol (-)-epigallocatechin gallate improve muscle function in a mouse model for duchenne muscular dystrophy. Am J Physiol Cell Physiol 2006;290:C616-25
  • Evans NP, Call JA, Bassaganya-Riera J, Green tea extract decreases muscle pathology and NF-kappaB immunostaining in regenerating muscle fibers of mdx mice. Clin Nutr 2010;29:391-8
  • Hibaoui Y, Reutenauer-Patte J, Patthey-Vuadens O, Melatonin improves muscle function of the dystrophic mdx5Cv mouse, a model for Duchenne muscular dystrophy. J Pineal Res 2011;51:163-71
  • Chahbouni M, Escames G, Lopez LC, Melatonin treatment counteracts the hyperoxidative status in erythrocytes of patients suffering from duchenne muscular dystrophy. Clin Biochem 2011;44:853-8
  • Sanchez-Barcelo EJ, Mediavilla MD, Tan DX, Clinical uses of melatonin: evaluation of human trials. Curr Med Chem 2010;17:2070-95
  • Gillis JC, Benefield P, McTavish D. Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders. Drugs Aging 1994;5:133-52
  • Buyse GM, Van der Mieren G, Erb M, Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performance. Eur Heart J 2009;30:116-24
  • Buyse GM, Goemans N, van den Hauwe M, Idebenone as a novel, therapeutic approach for duchenne muscular dystrophy: results from a 12 month, double-blind, randomized placebo-controlled trial. Neuromuscul Disord 2011;21:396-405
  • Lawler JM. Exacerbation of pathology by oxidative stress in respiratory and locomotor muscles with duchenne muscular dystrophy. J Physiol 2011;589:2161-70
  • Peterson JM, Guttridge DC. Skeletal muscle diseases, inflammation, and NF-kappaB signaling: insights and opportunities for therapeutic intervention. Int Rev Immunol 2008;27:375-87
  • Du J, Mitch WE, Wang X, Glucocorticoids induce proteasome C3 subunit expression in L6 muscle cells by opposing the suppression of its transcription by NF-kappa B. J Biol Chem 2000;275:19661-6
  • Grounds MD, Torrisi J. Anti-TNFalpha (Remicade) therapy protects dystrophic skeletal muscle from necrosis. FASEB J 2004;18:676-82
  • Pierno S, Nico B, Burdi R, Role of tumour necrosis factor alpha, but not of cyclo-oxygenase-2-derived eicosanoids, on functional and morphological indices of dystrophic progression in mdx mice: a pharmacological approach. Neuropathol Appl Neurobiol 2007;33:344-59
  • Hodgetts S, Radley H, Davies M, Reduced necrosis of dystrophic muscle by depletion of host neutrophils, or blocking TNFalpha function with Etanercept in mdx mice. Neuromuscul Disord 2006;16:591-602
  • Piers AT, Lavin T, Radley-Crabb HG, Blockade of TNF in vivo using cV1q antibody reduces contractile dysfunction of skeletal muscle in response to eccentric exercise in dystrophic mdx and normal mice. Neuromuscul Disord 2011;21:132-41
  • Paller AS, Siegfried EC, Langley RG, Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med 2008;358:241-51
  • Otten MH, Prince FH, Armbrust W, Factors associated with treatment response to etanercept in juvenile idiopathic arthritis. JAMA 2011;306:2340-7
  • Peterson JM, Kline W, Canan BD, Peptide-based inhibition of NF-kappaB rescues diaphragm muscle contractile dysfunction in a murine model of duchenne muscular dystrophy. Mol Med 2011;17:508-15
  • Delfin DA, Xu Y, Peterson JM, Improvement of cardiac contractile function by peptide-based inhibition of NF-kappaB in the utrophin/dystrophin-deficient murine model of muscular dystrophy. J Transl Med 2011;9:68
  • Mendell JR, Engel WK, Derrer EC. Duchenne muscular dystrophy: functional ischemia reproduces its characteristic lesions. Science 1971;172:1143-5
  • Percival JM, Anderson KN, Huang P, Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle. J Clin Invest 2010;120:816-26
  • Chang WJ, Iannaccone ST, Lau KS, Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proc Natl Acad Sci USA 1996;93:9142-7
  • Asai A, Sahani N, Kaneki M, Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phosphodiesterase-5 inhibitor therapy in mouse muscular dystrophy. PLoS ONE 2007;2:e806
  • Kobayashi YM, Rader EP, Crawford RW, Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature 2008;456:511-15
  • Khairallah M, Khairallah RJ, Young ME, Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. Proc Natl Acad Sci USA 2008;105:7028-33
  • Nagayama T, Zhang M, Hsu S, Sustained soluble guanylate cyclase stimulation offsets nitric-oxide synthase inhibition to restore acute cardiac modulation by sildenafil. J Pharmacol Exp Ther 2008;326:380-7
  • Fernhoff NB, Derbyshire ER, Marletta MA. A nitric oxide/cysteine interaction mediates the activation of soluble guanylate cyclase. Proc Natl Acad Sci USA 2009;106:21602-7
  • Wang G, Burczynski FJ, Hasinoff BB, Development of a nitric oxide-releasing analogue of the muscle relaxant guaifenesin for skeletal muscle satellite cell myogenesis. Mol Pharm 2009;6:895-904
  • Pisconti A, Brunelli S, Di Padova M, Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion. J Cell Biol 2006;172:233-44
  • Wehling M, Spencer MJ, Tidball JG. A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. J Cell Biol 2001;155:123-31
  • Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature 1990;346:274-6
  • Baerwald C, Verdecchia P, Duquesroix B, Efficacy, safety, and effects on blood pressure of naproxcinod 750 mg twice daily compared with placebo and naproxen 500 mg twice daily in patients with osteoarthritis of the hip: a randomized, double-blind, parallel-group, multicenter study. Arthritis Rheum 2010;62:3635-44
  • Schnitzer TJ, Hochberg MC, Marrero CE, Efficacy and safety of naproxcinod in patients with osteoarthritis of the knee: a 53-week prospective randomized multicenter study. Semin Arthritis Rheum 2011;40:285-97
  • Townsend R, Bittar N, Rosen J, Blood pressure effects of naproxcinod in hypertensive patients. J Clin Hypertens (Greenwich) 2011;13:376-84
  • White WB, Schnitzer TJ, Bakris GL, Effects of naproxcinod on blood pressure in patients with osteoarthritis. Am J Cardiol 2011;107:1338-45
  • Brunelli S, Sciorati C, D'Antona G, Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy. Proc Natl Acad Sci USA 2007;104:264-9
  • D'Angelo MG, Gandossini S, Martinelli Boneschi F, Nitric oxide donor and non steroidal anti inflammatory drugs as a therapy for muscular dystrophies: evidence from a safety study with pilot efficacy measures in adult dystrophic patients. Pharmacol Res 2012;65:472-9
  • Sampaolesi M, Blot S, D'Antona G, Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 2006;444:574-9

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