• Kevin M Flanigan, Thomas Voit, Xiomara Q Rosales, Laurent Servais, John E Kraus, Claire Wardell, Allison Morgan, Susie Dorricott, Joanna Nakielny, Naashika Quarcoo, Lia Liefaard, Tom Drury, Giles Campion, and Padraig Wright.
• Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, United States.
• Neuromuscul. Disord. 2014 Jan 1;24(1):16-24.

AbstractDuchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after a single subcutaneous administration in non-ambulatory subjects. Eligible subjects were non-ambulant boys aged ⩾9years, in wheelchairs for ⩾1 to ⩽4years, with a diagnosis of DMD resulting from a mutation correctable by drisapersen treatment. Four dose cohorts were planned (3, 6, 9 and 12mg/kg), but study objectives were met with the 9mg/kg dose. Less than proportional increase in exposure was demonstrated over the 3-9mg/kg dose range, though post hoc analysis showed dose proportionality was more feasible over the 3-6mg/kg range. Single doses of drisapersen at 3 and 6mg/kg did not result in significant safety or tolerability concerns; however, at the 9mg/kg dose, pyrexia and transient elevations in inflammatory parameters were seen. The maximum tolerated dose of 6mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population.Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

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