Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy

Neurology
Diane E FrankSKIP-NMD Study Group

Abstract

To report safety, pharmacokinetics, exon 53 skipping, and dystrophin expression in golodirsen-treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping. Part 1 was a randomized, double-blind, placebo-controlled, 12-week dose titration of once-weekly golodirsen; part 2 is an ongoing, open-label evaluation. Safety and pharmacokinetics were primary and secondary objectives of part 1. Primary biological outcome measures of part 2 were blinded exon skipping and dystrophin protein production on muscle biopsies (baseline, week 48) evaluated, respectively, using reverse transcription PCR and Western blot and immunohistochemistry. Twelve patients were randomized to receive golodirsen (n = 8) or placebo (n = 4) in part 1. All from part 1 plus 13 additional patients received 30 mg/kg golodirsen in part 2. Safety findings were consistent with those previously observed in pediatric patients with DMD. Most of the study drug was excreted within 4 hours following administration. A significant increase in exon 53 skipping was associated with ∼16-fold increase over baseline in dystrophin protein expression at week 48, with a mean percent normal dystrophin protein standard of 1.019% (range, 0.09%-4.30%). Sarcolemmal loc...Continue Reading

Associated Clinical Trials

References

Jan 1, 1991·Neuromuscular Disorders : NMD·A E Emery
Mar 7, 2002·Lancet·Alan E H Emery
Feb 8, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Steve D WiltonSusan Fletcher
Jan 15, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Linda J PopplewellIan R Graham
Jan 22, 2009·Human Mutation·Annemieke Aartsma-RusJohan T den Dunnen
Mar 17, 2009·Annals of Neurology·Toshifumi YokotaEric Hoffman
Dec 1, 2009·Lancet Neurology·Katharine BushbyUNKNOWN DMD Care Considerations Working Group
Mar 28, 2012·Annals of Neurology·Jerry R MendellRobert B Weiss
Feb 27, 2013·Annals of Neurology·Kevin M FlaniganUNKNOWN United Dystrophinopathy Project
Mar 6, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maaike van PuttenAnnemieke M Aartsma-Rus
Aug 3, 2013·Annals of Neurology·Jerry R MendellUNKNOWN Eteplirsen Study Group
May 2, 2014·Neuromuscular Disorders : NMD·Jean K MahNathalie Jette
Oct 13, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria Sofia FalzaranoAlessandra Ferlini
Nov 18, 2015·Annals of Neurology·Jerry R MendellUNKNOWN Eteplirsen Study Group and Telethon Foundation DMD Italian Network
Jun 28, 2016·Neurology·Luca BelloUNKNOWN CINRG investigators
Aug 16, 2016·Neuropsychiatric Disease and Treatment·Jean K Mah
Oct 18, 2016·American Journal of Human Genetics·Luca BelloUNKNOWN Cooperative International Neuromuscular Research Group
Dec 10, 2016·Journal of Perianesthesia Nursing : Official Journal of the American Society of PeriAnesthesia Nurses·Barbara A Alliod, Rebecca A Ash
Jan 7, 2018·Neuromuscular Disorders : NMD·Megan A WaldropKevin M Flanigan
Mar 12, 2019·Journal of Neuromuscular Diseases·Navid KhanUNKNOWN Eteplirsen Investigators and the CINRG DNHS Investigators

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Citations

Sep 5, 2020·Pediatric Pulmonology·Nicolas J Abreu, Megan A Waldrop
Sep 16, 2020·Pharmacological Reviews·Ai-Ming YuMei-Juan Tu
Jun 22, 2020·Muscle & Nerve·Paula R ClemensUNKNOWN CINRG BNHS Investigators
Jul 29, 2020·Biology Open·Janelle M SpinazzolaLouis M Kunkel
Jul 2, 2020·Journal of Clinical Medicine·Karishma DhuriRaman Bahal
Oct 20, 2020·Expert Opinion on Biological Therapy·Anne-Fleur E Schneider, Annemieke Aartsma-Rus
Oct 20, 2020·PloS One·Sarah R RiveraKatherine D Mathews
Oct 22, 2020·International Journal of Molecular Sciences·Kristin A HamSteve D Wilton
Oct 10, 2020·Annual Review of Pharmacology and Toxicology·C Frank BennettDon W Cleveland
Dec 18, 2020·Frontiers in Pediatrics·Marina Flotats-Bastardas, Andreas Hahn
Jan 31, 2021·International Journal of Molecular Sciences·Anna YangOrnit Chiba-Falek
Nov 8, 2020·Annals of Neurology·Yvan de FeraudyHelge Amthor
Jan 8, 2021·Orphanet Journal of Rare Diseases·Eve FouargeUNKNOWN NatHis-MTM Study Group
Feb 14, 2021·Neuroscience and Biobehavioral Reviews·Anthony Tucker-BartleyJaymin Upadhyay
Feb 20, 2021·Nature Reviews. Disease Primers·Dongsheng DuanAnnemieke Aartsma-Rus
Feb 19, 2021·The Journal of Biological Chemistry·Stanley T CrookeRosanne M Crooke
Mar 7, 2021·Journal of Clinical Medicine·Fernanda FortunatoAlessandra Ferlini
Mar 7, 2021·Muscle & Nerve·Natalie L GoedekerCraig M Zaidman
Mar 26, 2021·Nature Reviews. Drug Discovery·Stanley T CrookeXue-Hai Liang
Apr 6, 2021·Frontiers in Bioengineering and Biotechnology·Tulsi Ram DamaseJohn P Cooke
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhichao TangJingxin Wang
May 1, 2021·Biomedicines·Maria Gagliardi, Ana Tari Ashizawa
Apr 25, 2021·Seminars in Pediatric Neurology·Samuel J MackenzieJerry R Mendell
Apr 7, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Eunyoung Choi, Taeyoung Koo
Aug 18, 2020·Biochemical Pharmacology·Stanley T CrookeRichard S Geary
May 18, 2021·Neuropathology and Applied Neurobiology·Patricia Soblechero-MartínVirginia Arechavala-Gomeza
May 30, 2021·European Journal of Heart Failure·Maria A Restrepo-CordobaUNKNOWN European Genetic Cardiomyopathies Initiative Investigators (see online supplementary Appendix S1)
May 23, 2021·Trends in Pharmacological Sciences·Tufan GökirmakPunit P Seth
Jun 8, 2021·Journal of Neuromuscular Diseases·Yoshitsugu Aoki, Matthew J A Wood
Jun 22, 2021·JAMA Neurology·Stephen M ChrzanowskiPeter B Kang
Jun 29, 2021·Journal of Neuromuscular Diseases·Shin'ichi TakedaEric P Hoffman
Jul 21, 2021·Orphanet Journal of Rare Diseases·Margaux PoleurLaurent Servais
Aug 2, 2021·Molecular Aspects of Medicine·Manish PandeyGeetanjali Chawla
Aug 18, 2021·Pharmacology & Therapeutics·Ai-Ming Yu, Mei-Juan Tu

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Methods Mentioned

BETA
reverse transcription PCR
biopsies
biopsy
Assay
protein assay
antisense oligonucleotide

Clinical Trials Mentioned

NCT02310906

Software Mentioned

SAS
R

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