Next steps for the optimization of exon therapy for Duchenne muscular dystrophy

References

• Duan D, Goemans N, Takeda S, et al. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021 Feb 18;7(1):13.
   PubMed Web of Science ®Google Scholar
• Dj B, Bushby K, CM B, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018 Mar;17(3):251–267.
   PubMed Web of Science ®Google Scholar
• Syed YY. Eteplirsen: first global approval. Drugs. 2016 Nov;76(17):1699–1704.
   PubMed Web of Science ®Google Scholar
• Heo YA. Golodirsen: first approval. Drugs. 2020 Feb;80(3):329–333.
   PubMed Web of Science ®Google Scholar
• Dhillon S. Viltolarsen: first approval. Drugs. 2020 July 01;80(10):1027–1031.
   PubMed Web of Science ®Google Scholar
• Shirley M. Casimersen: first approval. Drugs. 2021 May;81(7):875–879.
   PubMed Web of Science ®Google Scholar
• Aartsma-Rus A, van Ommen GJ. Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications. Rna. 2007 Oct;13(10):1609–1624.
   PubMed Web of Science ®Google Scholar
• A-FE S, Aartsma-Rus A. Developments in reading frame restoring therapy approaches for Duchenne muscular dystrophy. Expert Opin Biol Ther. 2021 Mar 04;21(3):343–359.
   PubMed Web of Science ®Google Scholar
• Kurreck J. Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem. 2003 Apr;270(8):1628–1644.
   PubMedGoogle Scholar
• Phosphorothioates EF. Essential components of therapeutic oligonucleotides. Nucleic Acid Ther. 2014;24(6):374–387.
   PubMed Web of Science ®Google Scholar
• Järver P, O’Donovan L, Gait MJ. A chemical view of oligonucleotides for exon skipping and related drug applications. Nucleic Acid Ther. 2014 Feb;24(1):37–47.
   PubMed Web of Science ®Google Scholar
• Amantana A, Iversen PL. Pharmacokinetics and biodistribution of phosphorodiamidate morpholino antisense oligomers. Curr Opin Pharmacol. 2005 Oct;5(5):550–555.
   PubMed Web of Science ®Google Scholar
• Aartsma-Rus A, Kaman WE, Bremmer-Bout M, et al. Comparative analysis of antisense oligonucleotide analogs for targeted DMD exon 46 skipping in muscle cells. Gene Ther. 2004 Sep;11(18):1391–1398.
   PubMed Web of Science ®Google Scholar
• Heemskerk H, de Winter C, van Kuik P, et al. Preclinical PK and PD studies on 2’-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model. Mol Ther. 2010 Jun;18(6):1210–1217.
   PubMed Web of Science ®Google Scholar
• Yokota T, Hoffman E, Takeda S. Antisense oligo-mediated multiple exon skipping in a dog model of Duchenne muscular dystrophy. Methods Mol Biol. 2011;709:299–312.
   PubMedGoogle Scholar
• Yokota T, Lu QL, Partridge T, et al. Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann Neurol. 2009 Jun;65(6):667–676.
   PubMed Web of Science ®Google Scholar
• Shrewsbury SB, Sazani P, Muntoni F. P1.10 Comparative pharmacokinetics (PK) in primates and humans of AVI-4658, a phosphorodiamidate morpholino oligomer (PMO) for treating DMD patients. Neuromuscul Disord. 2011;21(9):644.
   Web of Science ®Google Scholar
• van Deutekom JC, Janson AA, Ginjaar IB, et al. Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med. 2007 Dec 27;357(26):2677–2686.
   PubMed Web of Science ®Google Scholar
• Goemans NM, Tulinius M, van den Akker JT, et al. Systemic administration of PRO051 in Duchenne’s muscular dystrophy. N Engl J Med. 2011 Apr 21;364(16):1513–1522.
   PubMed Web of Science ®Google Scholar
• Voit T, Topaloglu H, Straub V, et al. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014 Oct;13(10):987–996.
   PubMed Web of Science ®Google Scholar
• McDonald CM, Wong B, Flanigan KM, et al. Placebo-controlled phase 2 trial of drisapersen for Duchenne muscular dystrophy. Ann Clin Transl Neurol. 2018 Aug;5(8):913–926.
   PubMed Web of Science ®Google Scholar
• Goemans N, Mercuri E, Belousova E, et al. A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy. Neuromuscul Disord. 2018 Jan;28(1):4–15.
   PubMed Web of Science ®Google Scholar
• Kyndrisa: Withdrawal of the marketing authorisation application [Internet]. 2016 [cited 2022 Oct 24]. Available from: https://www.ema.europa.eu/en/medicines/human/withdrawn-applications/kyndrisa
   Google Scholar
• Declines FDA Approval for Drisapersen in DMD [Internet]. 2016 [cited 2022 Oct 24]. Available from: https://www.medscape.com/viewarticle/857406
   Google Scholar
• Wave life sciences announces discontinuation of suvodirsen development for Duchenne muscular dystrophy [internet]. 2019 [cited 2022 Oct 24]. Available from: https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-discontinuation-suvodirsen
   Google Scholar
• Rigo F, Hua Y, Chun SJ, et al. Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing. Nat Chem Biol. 2012 Apr 15;8(6):555–561.
   PubMed Web of Science ®Google Scholar
• Jirka SM, Tanganyika-de Winter CL, Jw B-VDM, et al. Evaluation of 2’-deoxy-2’-fluoro antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy. Mol Ther Nucleic Acids. 2015 Dec 1;4(12):e265.
   PubMedGoogle Scholar
• Chen S, Le BT, Chakravarthy M, et al. Systematic evaluation of 2’-Fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro. Sci Rep. 2019 Apr 15;9(1):6078.
   PubMedGoogle Scholar
• Kandasamy P, McClorey G, Shimizu M, et al. Control of backbone chemistry and chirality boost oligonucleotide splice switching activity. Nucleic Acids Res. 2022 Jun 10;50(10):5443–5466.
   PubMed Web of Science ®Google Scholar
• Wave Life Sciences Announces Initiation of Dosing in Phase 1b/2a clinical trial of WVE-N531 in Duchenne muscular dystrophy [internet]. 2021 [cited 2022 Oct 24]. Available from: https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-initiation-dosing-phase-1b2a
   Google Scholar
• Morita K, Hasegawa C, Kaneko M, et al. 2’-O,4’-C-ethylene-bridged nucleic acids (ENA) with nuclease-resistance and high affinity for RNA. Nucleic Acids Res Suppl. 2001;12(1):241–242
   Google Scholar
• Lee T, Awano H, Yagi M, et al. 2’-O-methyl RNA/ethylene-bridged nucleic acid chimera antisense oligonucleotides to induce dystrophin exon 45 skipping. Genes (Basel). 2017 Feb 10;8:2.
   Web of Science ®Google Scholar
• Ito K, Takakusa H, Kakuta M, et al. Renadirsen, a novel 2ʹOMeRNA/ENA(®) chimera antisense oligonucleotide, induces robust exon 45 skipping for dystrophin in vivo. Curr Issues Mol Biol. 2021 Sep 25;43(3):1267–1281.
   PubMed Web of Science ®Google Scholar
• Daiichi Sankyo Announces the Results Summary of Phase 1/2 Clinical Trial in Japan for DS-5141 [Internet]. 2021 [cited 2022 Oct 24]. Available from: https://www.daiichisankyo.com/media/press_release/detail/index_4112.html
   Google Scholar
• Kinali M, Arechavala-Gomeza V, Feng L, et al. Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 2009 Oct;8(10):918–928.
   PubMed Web of Science ®Google Scholar
• Cirak S, Arechavala-Gomeza V, Guglieri M, et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet. 2011 Aug 13;378(9791):595–605.
   PubMed Web of Science ®Google Scholar
• Mendell JR, Rodino-Klapac LR, Sahenk Z, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013 Nov;74(5):637–647.
   PubMed Web of Science ®Google Scholar
• Charleston JS, Schnell FJ, Dworzak J, et al. Eteplirsen treatment for Duchenne muscular dystrophy: exon skipping and dystrophin production. Neurology. 2018 Jun 12;90(24):e2146–e2154.
   PubMed Web of Science ®Google Scholar
• Mendell JR, Goemans N, Lowes LP, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016 Feb;79(2):257–271.
   PubMed Web of Science ®Google Scholar
• FDA grants accelerated approval to first drug for Duchenne muscular dystrophy [Internet]. 2016 [cited 2022 Oct 24]. Available from: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular-dystrophy
   Google Scholar
• Wang RT, Barthelemy F, Martin AS, et al. DMD genotype correlations from the Duchenne Registry: endogenous exon skipping is a factor in prolonged ambulation for individuals with a defined mutation subtype. Hum Mutat. 2018 Sep;39(9):1193–1202.
   PubMed Web of Science ®Google Scholar
• McDonald CM, Shieh PB, Abdel-Hamid HZ, et al., Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. J Neuromuscul Dis. 2021. 8(6): 989–1001.
   PubMedGoogle Scholar
• Frank DE, Schnell FJ, Akana C, et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology. 2020 May 26;94(21):e2270–e2282.
   PubMed Web of Science ®Google Scholar
• Servais L, Mercuri E, Straub V, et al. Long-term safety and efficacy data of golodirsen in ambulatory patients with Duchenne muscular dystrophy amenable to exon 53 skipping: a first-in-human, multicenter, two-part, open-label, phase 1/2 trial. Nucleic Acid Ther. 2022 Feb;32(1):29–39.
   PubMed Web of Science ®Google Scholar
• Iannaccone S, Phan H, Straub V, et al. P.132 casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: interim results from the phase 3 ESSENCE trial. Neuromuscul Disord. 2022 Oct 01;32:S102.
   Web of Science ®Google Scholar
• Komaki H, Nagata T, Saito T, et al. Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci Transl Med. 2018;10(437):eaan0713.
   PubMed Web of Science ®Google Scholar
• Clemens PR, Rao VK, Connolly AM, et al. Safety, tolerability, and efficacy of viltolarsen in boys with Duchenne muscular dystrophy amenable to exon 53 skipping: a phase 2 randomized clinical trial. JAMA Neurol. 2020 Aug 1;77(8):982–991.
   PubMed Web of Science ®Google Scholar
• Approves Targeted FDA Treatment for rare Duchenne muscular dystrophy mutation [internet]. 2020 [cited 2022 Oct 24]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation
   Google Scholar
• Clemens PR, Rao VK, Connolly AM, et al. Long-term functional efficacy and safety of viltolarsen in patients with Duchenne muscular dystrophy. J Neuromuscul Dis. 2022;9:493–501.
   PubMedGoogle Scholar
• Study shows the efficacy of antisense oligonucleotide-based exon 44 skipping drug, NS-089/NCNP-02, for patients with Duchenne muscular dystrophy (DMD) [Internet]. 2022 [cited 2022 Oct 24]. Available from: https://www.ncnp.go.jp/topics/2022/20220317e.html
   Google Scholar
• NS pharma pipeline [Internet]. [cited 2022 Oct 24]. Available from: https://www.nspharma.com/pipeline
   Google Scholar
• Moulton HM, Moulton JD. Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. Biochim Biophys Acta - Biomembr. 2010;1798(12):2296–2303.
   PubMed Web of Science ®Google Scholar
• Gan L, Wu LCL, Wood JA, et al. A cell-penetrating peptide enhances delivery and efficacy of phosphorodiamidate morpholino oligomers in mdx mice. Mol Ther Nucleic Acids. 2022;30:17–27.
   PubMedGoogle Scholar
• Clinical Update: Results from 30 mg/kg cohort of MOMENTUM study of SRP-5051 for Duchenne muscular dystrophy [internet]. 2021 [cited 2022 Oct 24]. Available from: https://investorrelations.sarepta.com/events/event-details/clinical-update-results-30-mgkg-cohort-momentum-study-srp-5051-duchenne
   Google Scholar
• Sheikh O, Yokota T. Pharmacology and toxicology of eteplirsen and SRP-5051 for DMD exon 51 skipping: an update. Arch Toxicol. 2022 Jan 01;96(1):1–9.
   PubMed Web of Science ®Google Scholar
• Sarepta therapeutics announces that FDA has lifted its clinical hold on SRP-5051 for the treatment of Duchenne muscular dystrophy [Internet]. 2022 [cited 2022 Oct 24]. Available from: https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-has-lifted-its-clinical-hold
   Google Scholar
• Tsoumpra MK, Fukumoto S, Matsumoto T, et al. Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases. EBioMedicine. 2019 Jul;45:630–645.
   PubMed Web of Science ®Google Scholar
• A novel enhanced delivery oligonucleotide (EDO) therapeutic demonstrates considerable potential in treating Duchenne muscular dystrophy [Internet]. [cited 2022 Oct 24]. Available from: https://pepgen.com/wp-content/uploads/2022/02/PepGen_A-novel-enhanced-delivery-oligonucleotide-EDO-therapeutic.pdf
   Google Scholar
• PepGen Announces First Participant Dosed in a Phase 1 Clinical Trial of PGN-EDO51 for the treatment of Duchenne muscular dystrophy [Internet]. 2022 [cited 2022 Oct 24]. Available from: https://investors.pepgen.com/news-releases/news-release-details/pepgen-announces-first-participant-dosed-phase-1-clinical-trial
   Google Scholar
• PepGen Reports Positive Data from Phase 1 Trial of PGN-EDO51 for the treatment of Duchenne muscular dystrophy [internet]. 2022 [cited 2022 Oct 24]. Available from: https://investors.pepgen.com/news-releases/news-release-details/pepgen-reports-positive-data-phase-1-trial-pgn-edo51-treatment
   Google Scholar
• Qian Z, LaRochelle JR, Jiang B, et al. Early endosomal escape of a cyclic cell-penetrating peptide allows effective cytosolic cargo delivery. Biochemistry. 2014 Jun 24;53(24):4034–4046.
   PubMed Web of Science ®Google Scholar
• Entrada therapeutics presents new data supporting its growing pipeline of endosomal escape vehicle (EEV™) Therapeutics at TIDES USA 2022 [Internet]. 2022 [cited 2022 Oct 24]. Available from: https://ir.entradatx.com/news-releases/news-release-details/entrada-therapeutics-presents-new-data-supporting-its-growing
   Google Scholar
• Desjardins CA, Yao M, Hall J, et al. Enhanced exon skipping and prolonged dystrophin restoration achieved by TfR1-targeted delivery of antisense oligonucleotide using FORCE conjugation in mdx mice. Nucleic Acids Res. 2022;50:11401–11414.
   PubMed Web of Science ®Google Scholar
• Avidity biosciences pipeline overview [Internet]. [cited 2022 Oct 24]. Available from: https://www.aviditybiosciences.com/pipeline/pipeline-overview/
   Google Scholar
• Systemic DD. AAV micro-dystrophin gene therapy for Duchenne muscular dystrophy. Mol Ther. 2018 Oct 3;26(10):2337–2356.
   PubMed Web of Science ®Google Scholar
• Potter RA, Griffin DA, Heller KN, et al. Dose-Escalation Study of Systemically Delivered rAAVrh74.MHCK7.micro-dystrophin in the mdx mouse model of Duchenne muscular dystrophy. Hum Gene Ther. 2021 Apr;32(7–8):375–389.
   PubMed Web of Science ®Google Scholar
• Mendell JR, Sahenk Z, Lehman K, et al. Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a nonrandomized controlled trial. JAMA Neurol. 2020 Sep 1;77(9):1122–1131.
   PubMed Web of Science ®Google Scholar
• Müller B, The SD. U7 snRNP and the hairpin binding protein: key players in histone mRNA metabolism. Semin Cell Dev Biol. 1997 Dec;8(6):567–576.
   PubMed Web of Science ®Google Scholar
• Schümperli D, Pillai RS. The special Sm core structure of the U7 snRNP: far-reaching significance of a small nuclear ribonucleoprotein. Cell Mol Life Sci. 2004 Oct;61(19–20):2560–2570.
   PubMed Web of Science ®Google Scholar
• Gorman L, Suter D, Emerick V, et al. Stable alteration of pre-mRNA splicing by modified U7 small nuclear RNAs. Proc Natl Acad Sci U S A. 1998;95(9):4929–4934.
   PubMed Web of Science ®Google Scholar
• Lesman D, Rodriguez Y, Rajakumar D, et al. U7 snRNA, a small RNA with a big impact in gene therapy. Hum Gene Ther. 2021 Nov;32(21–22):1317–1329.
   PubMed Web of Science ®Google Scholar
• Vulin A, Barthélémy I, Goyenvalle A, et al. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol Ther. 2012 Nov;20(11):2120–2133.
   PubMed Web of Science ®Google Scholar
• Goyenvalle A, Vulin A, Fougerousse F, et al. Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science. 2004 Dec 3;306(5702):1796–1799.
   PubMed Web of Science ®Google Scholar
• Aupy P, Zarrouki F, Sandro Q, et al. Long-term efficacy of AAV9-U7snRNA-mediated exon 51 skipping in mdx52 mice. Mol Ther Methods Clin Dev. 2020 Jun 12;17:1037–1047.
   PubMed Web of Science ®Google Scholar
• Zincarelli C, Soltys S, Rengo G, et al. Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart. Clin Transl Sci. 2010 Jun;3(3):81–89.
   PubMed Web of Science ®Google Scholar
• Wein N, Vulin A, Falzarano MS, et al. Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. Nat Med. 2014 Sep;20(9):992–1000.
   PubMed Web of Science ®Google Scholar
• Nationwide researchers announce restoration of full-length dystrophin in humans [internet]. 2022 [cited 2022 Oct 24]. Available from: https://cureduchenne.org/all-news/nationwide-researchers-announce-restoration-of-full-length-dystrophin-in-humans/
   Google Scholar
• Waldrop DM, Lawlor DM, Vetter TMD, et al. LATE BREAKING NEWS ORAL PRESENTATION: LBO 3 Expression of apparent full-length dystrophin in skeletal muscle in a first-in-human gene therapy trial using the scAAV9.U7-ACCA vector. Neuromuscul Disord. 2020;30:S166–S167.
   Web of Science ®Google Scholar
• Notice regarding impairment loss for products under development [internet]. 2022 [cited 2022 Oct 24]. Available from: https://www.astellas.com/en/news/25731
   Google Scholar
• JHFd B, Hoenderop JGJ, Bindels RJM. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1–46.
   PubMed Web of Science ®Google Scholar
• Lurio JG, Peay HL, Mathews KD. Recognition and management of motor delay and muscle weakness in children. Am Fam Physician. 2015 Jan 1;91(1):38–44.
   PubMed Web of Science ®Google Scholar
• Ke Q, Zhao Z-Y, Mendell JR, et al. Progress in treatment and newborn screening for Duchenne muscular dystrophy and spinal muscular atrophy. World J Pediatr. 2019 June 01;15(3):219–225.
   PubMed Web of Science ®Google Scholar
• PPMD submits RUSP nomination package for duchenne muscular dystrophy [Internet]. 2022 [cited 2022 Oct 24]. Available from: https://www.parentprojectmd.org/ppmd-submits-rusp-nomination-package-for-duchenne-muscular-dystrophy/
   Google Scholar
• Muntoni F, Signorovitch J, Sajeev G, et al. Real-world and natural history data for drug evaluation in Duchenne muscular dystrophy: suitability of the North Star ambulatory assessment for comparisons with external controls. Neuromuscul Disord. 2022 Apr;32(4):271–283.
   PubMed Web of Science ®Google Scholar
• Goemans N, Wong B, Van den Hauwe M, et al. Prognostic factors for changes in the timed 4-stair climb in patients with Duchenne muscular dystrophy, and implications for measuring drug efficacy: a multi-institutional collaboration. PLoS One. 2020;15(6):e0232870.
   PubMed Web of Science ®Google Scholar
• Merlini L, Sabatelli P. Improving clinical trial design for Duchenne muscular dystrophy. BMC Neurol. 2015 Aug;26(15):153.
   Google Scholar
• Straub V, Mercuri E, Aartsma-Rus A, et al. Report on the workshop: meaningful outcome measures for Duchenne muscular dystrophy, London, UK, 30–31 January 2017. Neuromuscular Disorders. 2018;28(8):690–701.
   Google Scholar