New pharmacotherapies for genetic neuromuscular disorders: opportunities and challenges

References

• Long C, Amoasii L, Bassel-Duby R, et al. Genome editing of monogenic neuromuscular diseases a systematic review. JAMA Neurol. 2016;73(11):1349–1355.
   PubMed Web of Science ®Google Scholar
• U.S. 97th Congress. Orphan Drug Act. Public Law 97-414, January 4, 1983.
   Google Scholar
• Bonne G, Rivier F, Hamroun D. The 2018 version of the gene table of monogenic neuromuscular disorders (nuclear genome). Neuromuscul Disord. 2017;27:1152–1183.
   PubMed Web of Science ®Google Scholar
• Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103–115.
   PubMed Web of Science ®Google Scholar
• Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular,rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251–267.
   PubMed Web of Science ®Google Scholar
• Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet J Rare Dis. 2017;12(1):124.
   PubMedGoogle Scholar
• Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155–165.
   PubMed Web of Science ®Google Scholar
• Wirth B, Brichta L, Schrank B, et al. Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number. Hum Genet. 2006;119(4):422–428.
   PubMed Web of Science ®Google Scholar
• Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027–1049.
   PubMed Web of Science ®Google Scholar
• D’Amico A, Mercuri E, Tiziano FD, et al. Spinal muscular atrophy. Orphanet J Rare Dis. 2011;6:71.
   PubMed Web of Science ®Google Scholar
• Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. 2018;28(3):197–207.
   PubMed Web of Science ®Google Scholar
• Hua Y, Vickers TA, Okunola HL, et al. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet. 2008;82(4):834–848.
   PubMed Web of Science ®Google Scholar
• Zanetta C, Riboldi G, Nizzardo M, et al. Molecular, genetic and stem cell-mediated therapeutic strategies for spinal muscular atrophy (SMA). J Cell Mol Med. 2014;18(2):187–196.
   PubMed Web of Science ®Google Scholar
• Singh NN, Howell MD, Androphy EJ, et al. How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy. Gene Ther. 2017;24(9):520–526.
   PubMed Web of Science ®Google Scholar
• Geary RS, Yu RZ, Levin AA. Pharmacokinetics of phosphorothioate antisense oligodeoxynucleotides. Curr Opin Investig Drugs. 2001;2(4):562–573.
   PubMedGoogle Scholar
• Monteith DK, Horner MJ, Gillett NA, et al. Evaluation of the renal effects of an antisense phosphorothioate oligodeoxynucleotide in monkeys. Toxicol Pathol. 1999;27(3):307–317.
   PubMed Web of Science ®Google Scholar
• Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends Mol Med. 2013;19:40–50.
   PubMed Web of Science ®Google Scholar
• Foust KD, Wang X, McGovern VL, et al. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010;28:271–274.
   PubMed Web of Science ®Google Scholar
• Wirth B, Martine B, Cecile M, et al. Moving towards treatments for spinal muscular atrophy: hopes and limits. Expert Opin Emerg Drugs. 2015;20(3):353–356.
   PubMed Web of Science ®Google Scholar
• Gidaro T, Servais L. Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps. Dev Med Child Neurol. 2019;61(1):19–24.
   PubMed Web of Science ®Google Scholar
• Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology. 2016;86(10):890–897.
   PubMed Web of Science ®Google Scholar
• Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017–3026.
   PubMed Web of Science ®Google Scholar
• Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625–635.
   PubMed Web of Science ®Google Scholar
• Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377(18):1723–1732.
   PubMed Web of Science ®Google Scholar
• Kariya S, Obis T, Garone C, et al. Requirement of enhanced survival motoneuron protein imposed during neuromuscular junction maturation. J Clin Invest. 2014;124:785–800.
   PubMed Web of Science ®Google Scholar
• cited [2019 Jun 10]. https://spinalnewsinternational.com/nurture-spinraza-sma
   Google Scholar
• Pechmann A, Langer T, Schorling D, et al. Evaluation of children with SMA type 1 under treatment with nusinersen within the expanded access program in Germany. J Neuromuscul Dis. 2018;5(2):135–143.
   PubMedGoogle Scholar
• Messina S, Pane M, Sansone V, et al. Expanded access program with nusinersen in SMA type I in Italy: strengths and pitfalls of a successful experience. Neuromuscul Disord. 2017;27(12):1084–1086.
   PubMed Web of Science ®Google Scholar
• Aragon-Gawinska K, Daron A, Gargaun E, et al. Nusinersen in spinal muscular atrophy type 1 patients older than 7 months: a cohort study. Neurology. 2018;91(14):e1312–e1318.
   PubMed Web of Science ®Google Scholar
• Farrar MA, Teoh HL, Carey KA, et al. Nusinersen for SMA: expanded access programme. J Neurol Neurosurg Psychiatry. 2018;89(9):937–942.
   PubMed Web of Science ®Google Scholar
• Meyer K, Ferraiuolo L, Schmelzer L, et al. Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates. Mol Ther. 2015;23(3):477–487.
   PubMed Web of Science ®Google Scholar
• Al-Zaidy S, Pickard AS, Kotha K, et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019;54(2):179–185.
   PubMed Web of Science ®Google Scholar
• Dabbous O, Maru B, Jansen JP, et al. Survival, motor function, and motor milestones: comparison of AVXS-101 relative to nusinersen for the treatment of infants with spinal muscular atrophy type 1. Adv Ther. 2019;36:1164–1176.
   PubMed Web of Science ®Google Scholar
• Vita G, Vita GL, Musumeci O, et al. Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 2: diseases of motor neuron and skeletal muscle. Neurol Sci. 2019;40(4):671–681.
   PubMed Web of Science ®Google Scholar
• Choudhury SR, Hudry E, Maguire CA, et al. Viral vectors for therapy of neurologic diseases. Neuropharmacology. 2017;120:63–80.
   PubMed Web of Science ®Google Scholar
• Ratni H, Ebeling M, Baird J, et al. Discovery of risdiplam, a selective survival of motor neuron-2 (SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA). J Med Chem. 2018;61(15):6501–6517.
   PubMed Web of Science ®Google Scholar
• Sturm S, Günther A, Jaber B, et al. A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier. Br J Clin Pharmacol. 2019;85(1):181–193.
   PubMed Web of Science ®Google Scholar
• cited [2019 Jun 10]. https://www.roche.com/media/releases/med-cor-2018-12-17.htm
   Google Scholar
• Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9(1):77–93.
   PubMed Web of Science ®Google Scholar
• D’Amico A, Catteruccia M, Baranello G, et al. Diagnosis of Duchenne muscular dystrophy in Italy in the last decade: critical issues and areas for improvements. Neuromuscul Disord. 2017;27(5):447–451.
   PubMed Web of Science ®Google Scholar
• Passamano L, Taglia A, Palladino A, et al. Improvement of survival in Duchenne muscular dystrophy: retrospective analysis of 835 patients. Acta Myol. 2012;31(2):121–125.
   PubMedGoogle Scholar
• Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17(4):347–361.
   PubMed Web of Science ®Google Scholar
• Guglieri M, Bushby K, McDermott MP, et al. Developing standardized corticosteroid treatment for Duchenne muscular dystrophy. Contemp Clin Trials. 2017;58:34–39.
   PubMed Web of Science ®Google Scholar
• McDonald CM, Henricson EK, Abresch RT, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet. 2018;391(10119):451–461.
   PubMed Web of Science ®Google Scholar
• Mah JK. An overview of recent therapeutics advances for Duchenne muscular dystrophy. Methods Mol Biol. 2018;1687:3–17.
   PubMedGoogle Scholar
• Bladen CL, Salgado D, Monges S, et al. The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat. 2015;36(4):395–402.
   PubMed Web of Science ®Google Scholar
• Zhang K, Yangb X, Lina G, et al. Molecular genetic testing and diagnosis strategies for dystrophinopathies in the era of next generation sequencing. Clin Chim Acta. 2019;491:66–73.
   PubMed Web of Science ®Google Scholar
• Flanigan KM, Dunn DM, von Niederhausern A, et al. Nonsense mutation-associated becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene. Human Mutat. 2011;32(3):299–308.
   PubMed Web of Science ®Google Scholar
• Finkel RS, Flanigan KM, Wong B, et al. Phase 2a study of ataluren-mediated dystrophin production in patients with non- sense mutation Duchenne muscular dystrophy. PLoS ONE. 2013;8(12):e81302.
   PubMed Web of Science ®Google Scholar
• Bushby K, Finkel R, Wong B, et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014;50(4):477–487.
   PubMed Web of Science ®Google Scholar
• McDonald CM, Henricson EK, Han JJ, et al. The 6 minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle Nerve. 2010;41(4):500–510.
   PubMed Web of Science ®Google Scholar
• McDonald CM, Campbell C, Torricelli RE, et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10101):1489–1498.
   PubMed Web of Science ®Google Scholar
• cited [2019 Jun 10]. http://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeuticsannounces-initial-data-patient-registry
   Google Scholar
• Stein CA, Castanotto D. FDA-approved oligonucleotide therapies in 2017. Mol Ther. 2017;25(5):1069–1075.
   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;90:e2146–e2154.
   PubMed Web of Science ®Google Scholar
• Arechavala-Gomeza V, Graham IR, Popplewell LJ, et al. Comparative analysis of antisense oligonucleotide sequences for targeted skipping of exon 51 during dystrophin pre-mRNA splicing in human muscle. Hum Gene Ther. 2007;18(9):798–810.
   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;74:637–647.
   PubMed Web of Science ®Google Scholar
• Aartsma-Rus A, Krieg AM. FDA approves eteplirsen for Duchenne muscular dystrophy: the next chapter in the Eteplirsen Saga. Nucleic Acid Ther. 2017;27(1):1–3.
   PubMed Web of Science ®Google Scholar
• Mendell JR, Goemans N, Lowes LP, et al. Eteplirsen Study Group and Telethon Foundation DMD Italian Network. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79(2):257–271.
   PubMed Web of Science ®Google Scholar
• Kinane TB, Mayer OH, Duda PW, et al. Long-term pulmonary function in Duchenne muscular dystrophy: comparison of eteplirsen-treated patients to natural history. J Neuromuscul Dis. 2018;5(1):47–58.
   PubMedGoogle Scholar
• Aartsma-Rus A, Goemans N. A sequel to the eteplirsen saga: eteplirsen is approved in the United States but was not approved in Europe. Nucleic Acid Ther. 2019;29(1):13–15.
   PubMed Web of Science ®Google Scholar
• Iwamoto N, Butler DCD, Svrzikapa N, et al. Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense. oligonucleotides. Nat Biotechnol. 2017;35(9):845–851.
   PubMed Web of Science ®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;39:1193–1202.
   PubMed Web of Science ®Google Scholar
• Rodrigues M, Yokota T. An overview of recent advances and clinical applications of exon skipping and splice modulation for muscular dystrophy and various genetic diseases. Methods Mol Biol. 2018;1828:31–55.
   PubMedGoogle 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:eaan0713.
   PubMed Web of Science ®Google Scholar
• Elverman M, Goddard MA, Mack D, et al. Long-term effects of systemic gene therapy in a canine model of myotubular myopathy. Muscle Nerve. 2017;56(5):943–953.
   PubMed Web of Science ®Google Scholar
• Kuntz N, Shieh P, Smith B, et al. O.17 ASPIRO phase 1/2 gene therapy trial in X-linked myotubular myopathy: preliminary safety and efficacy findings. Neuromuscul Disord. 2018;28(2):S91.
   Google Scholar
• Griffin JL. Infantile acid maltase deficiency. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(1):23–61.
   PubMedGoogle Scholar
• Van der Ploeg AT, Reuser AJ. Pompe’s disease. Lancet. 2008;372(9646):1342–1353.
   PubMed Web of Science ®Google Scholar
• Kishnani PS, Hwu WL, Mandel H, et al. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr. 2006;148(5):671–676.
   PubMed Web of Science ®Google Scholar
• Angelini C, Semplicini C, Ravaglia S, et al. Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years. J Neurol. 2012;259(5):952–958.
   PubMed Web of Science ®Google Scholar
• Kishnani PS, Corzo D, Nicolino M, et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68(2):99–109.
   PubMed Web of Science ®Google Scholar
• Schoser B, Stewart A, Kanters S, et al. Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa. J Neurol. 2017;264(4):621–630.
   PubMed Web of Science ®Google Scholar
• Case LE, Beckemeyer AA, Kishnani PS. Infantile Pompe disease on ERT: update on clinical presentation, musculoskeletal management, and exercise considerations. Am J Med Genet C Semin Med Genet. 2012;160(1):69–79.
   Google Scholar
• Messinger YH, Mendelsohn NJ, Rhead W, et al. Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. Genet Med. 2012;14(1):135–142.
   PubMed Web of Science ®Google Scholar
• Poelman E, Hoogeveen-Westerveld M, van Den Hout JMP, et al. Effects of immunomodulation in classic infantile Pompe patients with high antibody titers. Orphanet J Rare Dis. 2019;14(1):71–82.
   PubMedGoogle Scholar
• Pena LD, Barohn RJ, Byrne BJ, et al. Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: a phase 1, open-label, multicenter, multinational, ascending dose study. Neuromuscul Disord. 2019;29(3):167–186.
   PubMed Web of Science ®Google Scholar
• Parenti G, Fecarotta S, la Marca G, et al. A chaperone enhances blood α-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy. Mol Ther. 2014;22(11):2004–2012.
   PubMed Web of Science ®Google Scholar
• Corti M, Liberati C, Smith BK, et al. Safety of intradiaphragmatic delivery of adeno-associated virus-mediated alpha-glucosidase (rAAV1-CMVhGAA) gene therapy in children affected by Pompe disease. Hum Gene Ther Clin Dev. 2017;28(4):208–218.
   PubMed Web of Science ®Google Scholar
• Lee JE, Cooper TA. Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans. 2009;37:1281–1286.
   PubMed Web of Science ®Google Scholar
• De Antonio M, Dogan C, Hamroun D, et al. Unravelling the myotonic dystrophy type 1 clinical spectrum: a systematic registry-based study with implications for disease classification. Rev Neurol (Paris). 2016;72(10):572–580.
   Google Scholar
• Jauvin D, Chrétien J, Pandey SK, et al. Targeting DMPK with antisense oligonucleotide improves muscle strength in myotonic dystrophy type 1 mice. Mol Ther Nucleic Acids. 2017;7:465–474.
   PubMedGoogle Scholar
• Matsui M, Corey DR. Non-coding RNAs as drug targets. Nat Rev Drug Discov. 2017;16(3):167–179.
   PubMed Web of Science ®Google Scholar
• Pandey SK, Wheeler TM, Justice SL, et al. Identification and characterization of modified antisense oligonucleotides targeting DMPK in mice and nonhuman primates for the treatment of myotonic dystrophy type 1. J Pharmacol Exp Ther. 2015;355:329–340.
   PubMed Web of Science ®Google Scholar
• Bassez G, Audureau E, Hogrel JY, et al. Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial. Brain. 2018;141(10):2855–2865.
   PubMedGoogle Scholar
• Broomfield A, Fletcher J, Davison J. Response of 33 UK patients with infantile-onset Pompe disease to enzyme replacement therapy. J Inherit Metab Dis. 2016;39(2):261–271.
   PubMed Web of Science ®Google Scholar
• Simoens S, Huys I. Market access of Spinraza (Nusinersen) for spinal muscular atrophy: intellectual property rights, pricing, value and coverage considerations. Gene Ther. 2017;24(9):539–541.
   PubMed Web of Science ®Google Scholar
• Sansone V, Albamonte E, Salmin F, et al. Intrathecal nusinersen treatment for SMA in a dedicated neuromuscular clinic: an example of multidisciplinary and integrated care. Neurol Sci. 2019;40(2):327–332.
   PubMed Web of Science ®Google Scholar
• Wurster CD, Winter B, Wollinsky K, et al. Intrathecal administration of nusinersen in adolescent and adult SMA type 2 and 3 patients. J Neurol. 2019;266(1):183–194.
   PubMed Web of Science ®Google Scholar
• Boardman FK, Sadler C, Young PJ. Newborn genetic screening for spinal muscular atrophy in the UK: the views of the general population. Mol Genet Genomic Med. 2018;6(1):99–108.
   PubMed Web of Science ®Google Scholar
• Ross LF, Clarke AJ. A historical and current review of newborn screening for neuromuscular disorders from around the world: lessons for the United States. Pediatr Neurol. 2017;77:12–22.
   PubMed Web of Science ®Google Scholar
• Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol. 2018;17(5):445–455.
   PubMed Web of Science ®Google Scholar
• Van der Ploeg AT, Kruijshaar ME, Toscano A, et al. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10 year experience. Eur J Neurol. 2017;24(6):768–e31.
   PubMed Web of Science ®Google Scholar
• Ramsey D, Scoto M, Mayhew A, et al. Revised Hammersmith scale for spinal muscular atrophy: a SMA specific clinical outcome assessment tool. PLoS One. 2017;12(2):e0172346.
   PubMed Web of Science ®Google Scholar
• DMD outcome measure study group, Straub V, Mercuri E. Report on the workshop: meaningful outcome measures for Duchenne muscular dystrophy, London, UK, 30–31 January 2017. Neuromuscul Disord. 2018;28(8):690–701.
   PubMed Web of Science ®Google Scholar
• Ricci F, Brusa C, Rossi F, et al. Functional assessment tools in children with Pompe disease: a pilot comparative study to identify suitable outcome measures for the standard of care. Eur J Paediatr Neurol. 2018;22(6):1103–1109.
   PubMed Web of Science ®Google Scholar