Meeting Report: New Directions in Biology and Disease of Skeletal Muscle 2014

Wyatt, Eugene; Sweeney, H. Lee; McNally, Elizabeth M.

doi:10.3233/jnd-149003

Cited by 1 publication

(1 citation statement)

References 86 publications

(82 reference statements)

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“…Newer agents including givinostat (NCT01761292), a histone deacetylase inhibitor; 125 CAT1004 (NCT02439216), an oral molecule that inhibits activated NF-κB; and flavocoxid (NCT01335295), a blend of plant-derived flavonoids with anti-inflammatory activity, are currently under evaluation as potential disease-modifying treatment for DMD. 126 , 127 …”

Section: Therapeutic Strategies For Dmdmentioning

confidence: 99%

Current and emerging treatment strategies for Duchenne muscular dystrophy

Mah

2016

NDT

103

122

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Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying mutations using new gene-editing technologies and corticosteroid analogs with better safety profiles offers renewed hope for many individuals with DMD and their families.

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Section: Therapeutic Strategies For Dmdmentioning

confidence: 99%