Histological effects of givinostat in boys with Duchenne muscular dystrophy

Paolo Bettica, Stefania Petrini, Valentina D'Oria, Adele D'Amico, Michela Catteruccia, Marika Pane, Serena Sivo, Francesca Magri, Simona Brajkovic, Sonia Messina, Gian Luca Vita, Barbara Gatti, Maurizio Moggio, Pier Lorenzo Puri, Maurizio Rocchetti, Giuseppe De Nicolao, Giuseppe Vita, Giacomo P. Comi, Enrico Bertini, Eugenio Mercuri

Research output: Contribution to journalArticle

Abstract

Duchenne Muscular Dystrophy (DMD) is caused by mutations in the dystrophin gene leading to dystrophin deficiency, muscle fiber degeneration and progressive fibrotic replacement of muscles. Givinostat, a histone deacetylase (HDAC) inhibitor, significantly reduced fibrosis and promoted compensatory muscle regeneration in mdx mice. This study was conducted to evaluate whether the beneficial histological effects of Givinostat could be extended to DMD boys. Twenty ambulant DMD boys aged 7 to <11 years on stable corticosteroid treatment were enrolled in the study and treated for ≥12 months with Givinostat. A muscle biopsy was collected at the beginning and at the end of treatment to evaluate the amount of muscle and fibrotic tissue. Histological effects were the primary objectives of the study. Treatment with Givinostat significantly increased the fraction of muscle tissue in the biopsies and reduced the amount of fibrotic tissue. It also substantially reduced tissue necrosis and fatty replacement. Overall the drug was safe and tolerated. Improvement in functional tests was not observed in this study, but the sample size of the study was not sufficient to draw definitive conclusions. This study showed that treatment with Givinostat for more than 1 year significantly counteracted histological disease progression in ambulant DMD boys aged 7 to 10 years.

Original languageEnglish
Pages (from-to)643-649
Number of pages7
JournalNeuromuscular Disorders
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

Keywords

  • Clinical trial
  • Duchenne muscular dystrophy
  • Givinostat
  • Histology
  • Histone deacetylase inhibitor

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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  • Cite this

    Bettica, P., Petrini, S., D'Oria, V., D'Amico, A., Catteruccia, M., Pane, M., Sivo, S., Magri, F., Brajkovic, S., Messina, S., Vita, G. L., Gatti, B., Moggio, M., Puri, P. L., Rocchetti, M., De Nicolao, G., Vita, G., Comi, G. P., Bertini, E., & Mercuri, E. (2016). Histological effects of givinostat in boys with Duchenne muscular dystrophy. Neuromuscular Disorders, 26(10), 643-649. https://doi.org/10.1016/j.nmd.2016.07.002