T.P.5.02 Pentoxifylline treatment fails to rescue muscle strength and function deterioration in prednisone-treated Duchenne muscular dystrophy (DMD)

Escolar, Diana M.; Gorni, Ksenija; Tesi-Rocha, A.C.; Mah, Jean K.; Nevo, Yoram; Korengberg, A.; Kolski, Hanna; Bertorini, Tulio E.; Connolly, Anne M.; Kuntz, Nancy L.; Zimmerman, Angela; Morgenroth, L.; Arrieta, Adrienne; Mayhew, J.; Florence, Julaine; Nei, Lei; Hu, Fengming; Henricson, E.; Leshner, Robert T.; Dubrovsky, Alberto

doi:10.1016/j.nmd.2008.06.343

Cited by 3 publications

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“…Untreated control mdx BAMs were run in each experiment, and any drift from their test day 0 plateau value was used to correct the response of the test groups as described in Materials and Methods. provement in muscle strength in prednisone-treated DMD patients who were also treated for 12 mo with the antifibrotic drug pentoxifylline (21); likewise, in mdx mBAMs, there was no improvement seen in prednisone-stimulated tetanic force with pentoxifylline ( Fig. 6B).…”

Section: Resultsmentioning

confidence: 89%

Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts

et al. 2009

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Identification of factors that improve muscle function in boys with Duchenne muscular dystrophy (DMD) could lead to an improved quality of life. To establish a functional in vitro assay for muscle strength, mdx murine myoblasts, the genetic homologue of DMD, were tissue engineered in 96-microwell plates into 3-dimensional muscle constructs with parallel arrays of striated muscle fibers. When electrically stimulated, they generated tetanic forces measured with an automated motion tracking system. Thirty-one compounds of interest as potential treatments for patients with DMD were tested at 3 to 6 concentrations. Eleven of the compounds (insulin-like growth factor-1, creatine, beta-hydroxy-beta-methylbutyrate, trichostatin A, lisinopril, and 6 from the glucocorticoid family) significantly increased tetanic force relative to placebo-treated controls. The glucocorticoids methylprednisolone, deflazacort, and prednisone increased tetanic forces at low doses (EC(50) of 6, 19, and 56 nM, respectively), indicating a direct muscle mechanism by which they may be benefitting DMD patients. The tetanic force assay also identified beneficial compound interactions (arginine plus deflazacort and prednisone plus creatine) as well as deleterious interactions (prednisone plus creatine inhibited by pentoxifylline) of combinatorial therapies taken by some DMD patients. Since mdx muscle in vivo and DMD patients respond in a similar manner to many of these compounds, the in vitro assay will be a useful tool for the rapid identification of new potential treatments for muscle weakness in DMD and other muscle disorders.

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Section: Resultsmentioning

confidence: 89%

Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts

et al. 2009

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“…91 A larger, randomized, controlled trial of pentoxifylline in boys older than 7 years of age who have DMD and were on prednisone, suggested no additional benefit over corticosteroids. 92 Development of more selective NF-B modulators is clearly warranted.…”

Section: Emerging Therapeutic Targetsmentioning

confidence: 99%

Approaching a New Age in Duchenne Muscular Dystrophy Treatment

Wagner

2008

Neurotherapeutics

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Summary:Duchenne muscular dystrophy is the most common and severe form of muscular dystrophy. The cornerstones of current treatment include corticosteroids for skeletal muscle weakness, afterload reduction for cardiomyopathy, and noninvasive ventilation for respiratory failure. With these interventions, patients are walking and living longer. However, the current status is still far from adequate. Increased private and federal funding of studies in Duchenne muscular dystrophy has led to a large number of novel agents with propitious therapeutic potential. These include agents that modify dystrophin expression, increase muscle growth and regeneration, and modulate inflammatory responses. Many of these agents are already in clinical trials. Challenges to the development of additional novel therapeutics exist, including lack of validated animal models and lack of adequate biomarkers as surrogate endpoints. However, these challenges are not insurmountable and the next decade will likely see meaningful, new treatment options introduced into the clinical care of patients with Duchenne muscular dystrophy.

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Two siblings with limb-girdle muscular dystrophy type 2E responsive to deflazacort

Wong‐Kisiel

Kuntz

2010

Neuromuscular Disorders

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T.P.5.02 Pentoxifylline treatment fails to rescue muscle strength and function deterioration in prednisone-treated Duchenne muscular dystrophy (DMD)

Cited by 3 publications

References 0 publications

Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts

Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts

Approaching a New Age in Duchenne Muscular Dystrophy Treatment

Two siblings with limb-girdle muscular dystrophy type 2E responsive to deflazacort

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