Histological effects of givinostat in boys with Duchenne muscular dystrophy

• DOI: 10.1016/j.nmd.2016.07.002
• Publication Date: 2016-07-12T23:43:15Z
• Authors: 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
• Keywords: Duchenne muscular dystrophy; Male; Histology; Clinical Neurology; 610; Motor Activity; 03 medical and health sciences; Adrenal Cortex Hormones; Clinical trial; Duchenne muscular dystrophy; Givinostat; Histology; Histone deacetylase inhibitor; Pediatrics, Perinatology and Child Health; Neurology; Neurology (clinical); Genetics (clinical); Humans; Genetics(clinical); Pediatrics, Perinatology, and Child Health; Child; Muscle, Skeletal; Histone deacetylase inhibitor; 0303 health sciences; Clinical trial; Duchenne muscular dystrophy; Givinostat; Histology; Histone deacetylase inhibitor; Dose-Response Relationship, Drug; Platelet Count; 3. Good health; Clinical trial; Histone Deacetylase Inhibitors; Muscular Dystrophy, Duchenne; Treatment Outcome; Neurology; Givinostat; Carbamates

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