Generic placeholder image

Current Pharmaceutical Design

Author(s): Mathilde Beaufils, Lauriane Travard, John Rendu and Isabelle Marty*

DOI: 10.2174/1389201022666210910102516

DownloadDownload PDF Flyer Cite As
Therapies for RYR1-Related Myopathies: Where We Stand and the Perspectives

Page: [15 - 25] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

RyR1-related myopathies are a family of genetic neuromuscular diseases due to mutations in the RYR1 gene. No treatment exists for any of these myopathies today, which could change in the coming years with the growing number of studies dedicated to the pre-clinical assessment of various approaches, from pharmacological to gene therapy strategies, using the numerous models developed up to now. In addition, the first clinical trials for these rare diseases have just been completed or are being launched. We review the most recent results obtained for the treatment of RyR1-related myopathies, and, in view of the progress in therapeutic development for other myopathies, we discuss the possible future therapeutic perspectives for RyR1-related myopathies.

Keywords: Ryanodine receptor, myopathy, pharmacological therapy, gene therapy, calcium, skeletal muscle, excitation-contraction coupling

[1]
Dulhunty AF, Beard NA, Casarotto MG. Recent advances in understanding the ryanodine receptor calcium release channels and their role in calcium signalling. F1000Res 2018; 7 F1000 Faculty Rev-1851.
[2]
Meissner G. Regulation of ryanodine receptor ion channels through posttranslational modifications. Curr Top Membr 2010; 66: 91-113.
[http://dx.doi.org/10.1016/S1063-5823(10)66005-X] [PMID: 21666757]
[3]
Mori F, Fukaya M, Abe H, Wakabayashi K, Watanabe M. Developmental changes in expression of the three ryanodine receptor mRNAs in the mouse brain. Neurosci Lett 2000; 285(1): 57-60.
[http://dx.doi.org/10.1016/S0304-3940(00)01046-6] [PMID: 10788707]
[4]
Pehlivan D, Bayram Y, Gunes N, et al. The genomics of arthrogryposis, a complex trait: Candidate genes and further evidence for oligogenic inheritance. Am J Hum Genet 2019; 105(1): 132-50.
[http://dx.doi.org/10.1016/j.ajhg.2019.05.015] [PMID: 31230720]
[5]
Bertocchini F, Ovitt CE, Conti A, et al. Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles. EMBO J 1997; 16(23): 6956-63.
[http://dx.doi.org/10.1093/emboj/16.23.6956] [PMID: 9384575]
[6]
Balschun D, Wolfer DP, Bertocchini F, et al. Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning. EMBO J 1999; 18(19): 5264-73.
[http://dx.doi.org/10.1093/emboj/18.19.5264] [PMID: 10508160]
[7]
Eckhardt J, Bachmann C, Sekulic-Jablanovic M, et al. Extraocular muscle function is impaired in ryr3-/- mice. J Gen Physiol 2019; 151(7): 929-43.
[http://dx.doi.org/10.1085/jgp.201912333] [PMID: 31085573]
[8]
Maryon EB, Coronado R, Anderson P. unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction. J Cell Biol 1996; 134(4): 885-93.
[http://dx.doi.org/10.1083/jcb.134.4.885] [PMID: 8769414]
[9]
Sullivan KM, Scott K, Zuker CS, Rubin GM. The ryanodine receptor is essential for larval development in Drosophila melanogaster. Proc Natl Acad Sci USA 2000; 97(11): 5942-7.
[http://dx.doi.org/10.1073/pnas.110145997] [PMID: 10811919]
[10]
Wu HH, Brennan C, Ashworth R. Ryanodine receptors, a family of intracellular calcium ion channels, are expressed throughout early vertebrate development. BMC Res Notes 2011; 4: 541.
[http://dx.doi.org/10.1186/1756-0500-4-541] [PMID: 22168922]
[11]
Takekura H, Sun X, Franzini-Armstrong C. Development of the excitation-contraction coupling apparatus in skeletal muscle: peripheral and internal calcium release units are formed sequentially. J Muscle Res Cell Motil 1994; 15(2): 102-18.
[http://dx.doi.org/10.1007/BF00130422] [PMID: 8051285]
[12]
Marty I, Fauré J. Excitation-contraction coupling alterations in myopathies. J Neuromuscul Dis 2016; 3(4): 443-53.
[http://dx.doi.org/10.3233/JND-160172] [PMID: 27911331]
[13]
Goonasekera SA, Beard NA, Groom L, et al. Triadin binding to the C-terminal luminal loop of the ryanodine receptor is important for skeletal muscle excitation contraction coupling. J Gen Physiol 2007; 130(4): 365-78.
[http://dx.doi.org/10.1085/jgp.200709790] [PMID: 17846166]
[14]
Lawal TA, Todd JJ, Witherspoon JW, et al. Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature. Skelet Muscle 2020; 10(1): 32.
[http://dx.doi.org/10.1186/s13395-020-00243-4] [PMID: 33190635]
[15]
Roux-Buisson N, Monnier N, Sagui E, et al. Identification of variants of the ryanodine receptor type 1 in patients with exertional heat stroke and positive response to the malignant hyperthermia in vitro contracture test. Br J Anaesth 2016; 116(4): 566-8.
[http://dx.doi.org/10.1093/bja/aew047] [PMID: 26994242]
[16]
Witting N, Laforêt P, Voermans NC, et al. Phenotype and genotype of muscle ryanodine receptor rhabdomyolysis-myalgia syndrome. Acta Neurol Scand 2018; 137(5): 452-61.
[http://dx.doi.org/10.1111/ane.12885] [PMID: 29635721]
[17]
Monnier N, Romero NB, Lerale J, et al. Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor. Hum Mol Genet 2001; 10(22): 2581-92.
[http://dx.doi.org/10.1093/hmg/10.22.2581] [PMID: 11709545]
[18]
Galleni Leão L, Santos Souza L, Nogueira L, et al. Dominant or recessive mutations in the RYR1 gene causing central core myopathy in Brazilian patients. Acta Myol 2020; 39(4): 274-82.
[PMID: 33458582]
[19]
Amburgey K, Bailey A, Hwang JH, et al. Genotype-phenotype correlations in recessive RYR1-related myopathies. Orphanet J Rare Dis 2013; 8: 117.
[http://dx.doi.org/10.1186/1750-1172-8-117] [PMID: 23919265]
[20]
Garibaldi M, Rendu J, Brocard J, et al. ‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies. Acta Neuropathol Commun 2019; 7(1): 3.
[http://dx.doi.org/10.1186/s40478-018-0655-5] [PMID: 30611313]
[21]
Lawal TA, Todd JJ, Meilleur KG. Ryanodine receptor 1-related myopathies: Diagnostic and therapeutic approaches. Neurotherapeutics 2018; 15(4): 885-99.
[http://dx.doi.org/10.1007/s13311-018-00677-1] [PMID: 30406384]
[22]
Amburgey K, McNamara N, Bennett LR, McCormick ME, Acsadi G, Dowling JJ. Prevalence of congenital myopathies in a representative pediatric united states population. Ann Neurol 2011; 70(4): 662-5.
[http://dx.doi.org/10.1002/ana.22510] [PMID: 22028225]
[23]
Pelletier L, Petiot A, Brocard J, et al. In vivo RyR1 reduction in muscle triggers a core-like myopathy. Acta Neuropathol Commun 2020; 8(1): 192.
[http://dx.doi.org/10.1186/s40478-020-01068-4] [PMID: 33176865]
[24]
Wei L, Salahura G, Boncompagni S, et al. Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease. FASEB J 2011; 25(9): 3068-78.
[http://dx.doi.org/10.1096/fj.11-187252] [PMID: 21646399]
[25]
Durham WJ, Aracena-Parks P, Long C, et al. RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice. Cell 2008; 133(1): 53-65.
[http://dx.doi.org/10.1016/j.cell.2008.02.042] [PMID: 18394989]
[26]
Dowling JJ, Arbogast S, Hur J, et al. Oxidative stress and successful antioxidant treatment in models of RYR1-related myopathy. Brain 2012; 135(Pt 4): 1115-27.
[http://dx.doi.org/10.1093/brain/aws036] [PMID: 22418739]
[27]
Michelucci A, De Marco A, Guarnier FA, Protasi F, Boncompagni S. Antioxidant treatment reduces formation of structural cores and improves muscle function in RYR1Y522S/WT mice. Oxid Med Cell Longev 2017; 2017: 6792694.
[http://dx.doi.org/10.1155/2017/6792694] [PMID: 29062463]
[28]
Todd JJ, Lawal TA, Witherspoon JW, et al. Randomized controlled trial of N-acetylcysteine therapy for RYR1-related myopathies. Neurology 2020; 94(13): e1434-44.
[http://dx.doi.org/10.1212/WNL.0000000000008872] [PMID: 31941795]
[29]
Brillantes AB, Ondrias K, Scott A, et al. Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein. Cell 1994; 77(4): 513-23.
[http://dx.doi.org/10.1016/0092-8674(94)90214-3] [PMID: 7514503]
[30]
Ahern GP, Junankar PR, Dulhunty AF. Subconductance states in single-channel activity of skeletal muscle ryanodine receptors after removal of FKBP12. Biophys J 1997; 72(1): 146-62.
[http://dx.doi.org/10.1016/S0006-3495(97)78654-5] [PMID: 8994600]
[31]
Chelu MG, Danila CI, Gilman CP, Hamilton SL. Regulation of ryanodine receptors by FK506 binding proteins. Trends Cardiovasc Med 2004; 14(6): 227-34.
[http://dx.doi.org/10.1016/j.tcm.2004.06.003] [PMID: 15451514]
[32]
Bellinger AM, Reiken S, Dura M, et al. Remodeling of ryanodine receptor complex causes “leaky” channels: a molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci USA 2008; 105(6): 2198-202.
[http://dx.doi.org/10.1073/pnas.0711074105] [PMID: 18268335]
[33]
Mei Y, Xu L, Kramer HF, Tomberlin GH, Townsend C, Meissner G. Stabilization of the skeletal muscle ryanodine receptor ion channel-FKBP12 complex by the 1,4-benzothiazepine derivative S107. PLoS One 2013; 8(1): e54208.
[http://dx.doi.org/10.1371/journal.pone.0054208] [PMID: 23349825]
[34]
Bellinger AM, Reiken S, Carlson C, et al. Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat Med 2009; 15(3): 325-30.
[http://dx.doi.org/10.1038/nm.1916] [PMID: 19198614]
[35]
Andersson DC, Betzenhauser MJ, Reiken S, et al. Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging. Cell Metab 2011; 14(2): 196-207.
[http://dx.doi.org/10.1016/j.cmet.2011.05.014] [PMID: 21803290]
[36]
Kushnir A, Todd JJ, Witherspoon JW, et al. Intracellular calcium leak as a therapeutic target for RYR1-related myopathies. Acta Neuropathol 2020; 139(6): 1089-104.
[http://dx.doi.org/10.1007/s00401-020-02150-w] [PMID: 32236737]
[37]
Aizpurua JM, Miranda JI, Irastorza A, et al. Discovery of a novel family of FKBP12 “reshapers” and their use as calcium modulators in skeletal muscle under nitro-oxidative stress. Eur J Med Chem 2021; 213: 113160.
[http://dx.doi.org/10.1016/j.ejmech.2021.113160] [PMID: 33493827]
[38]
Dirksen RT, Avila G. Altered ryanodine receptor function in central core disease: leaky or uncoupled Ca(2+) release channels? Trends Cardiovasc Med 2002; 12(5): 189-97.
[http://dx.doi.org/10.1016/S1050-1738(02)00163-9] [PMID: 12161072]
[39]
Loy RE, Orynbayev M, Xu L, et al. Muscle weakness in Ryr1I4895T/WT knock-in mice as a result of reduced ryanodine receptor Ca2+ ion permeation and release from the sarcoplasmic reticulum. J Gen Physiol 2011; 137(1): 43-57.
[http://dx.doi.org/10.1085/jgp.201010523] [PMID: 21149547]
[40]
Lee CS, Hanna AD, Wang H, et al. A chemical chaperone improves muscle function in mice with a RyR1 mutation. Nat Commun 2017; 8: 14659.
[http://dx.doi.org/10.1038/ncomms14659] [PMID: 28337975]
[41]
Volpatti JR, Endo Y, Knox J, et al. Identification of drug modifiers for RYR1-related myopathy using a multi-species discovery pipeline. eLife 2020; 9: e52946.
[http://dx.doi.org/10.7554/eLife.52946] [PMID: 32223895]
[42]
Kwok TCY, Ricker N, Fraser R, et al. A small-molecule screen in C. elegans yields a new calcium channel antagonist. Nature 2006; 441(7089): 91-5.
[http://dx.doi.org/10.1038/nature04657] [PMID: 16672971]
[43]
Rebbeck RT, Essawy MM, Nitu FR, et al. High-throughput screens to discover small-molecule modulators of ryanodine receptor calcium release channels. SLAS Discov 2017; 22(2): 176-86.
[http://dx.doi.org/10.1177/1087057116674312] [PMID: 27760856]
[44]
Andersson DC, Marks AR. Fixing ryanodine receptor Ca leak - a novel therapeutic strategy for contractile failure in heart and skeletal muscle. Drug Discov Today Dis Mech 2010; 7(2): e151-7.
[http://dx.doi.org/10.1016/j.ddmec.2010.09.009] [PMID: 21113427]
[45]
Aracena P, Tang W, Hamilton SL, Hidalgo C. Effects of S-glutathionylation and S-nitrosylation on calmodulin binding to triads and FKBP12 binding to type 1 calcium release channels. Antioxid Redox Signal 2005; 7(7-8): 870-81.
[http://dx.doi.org/10.1089/ars.2005.7.870] [PMID: 15998242]
[46]
Blayney LM, Jones J-L, Griffiths J, Lai FA. A mechanism of ryanodine receptor modulation by FKBP12/12.6, protein kinase A, and K201. Cardiovasc Res 2010; 85(1): 68-78.
[http://dx.doi.org/10.1093/cvr/cvp273] [PMID: 19661110]
[47]
Oda T, Yang Y, Uchinoumi H, et al. Oxidation of ryanodine receptor (RyR) and calmodulin enhance Ca release and pathologically alter, RyR structure and calmodulin affinity. J Mol Cell Cardiol 2015; 85: 240-8.
[http://dx.doi.org/10.1016/j.yjmcc.2015.06.009] [PMID: 26092277]
[48]
Uchinoumi H, Yang Y, Oda T, et al. CaMKII-dependent phosphorylation of RyR2 promotes targetable pathological RyR2 conformational shift. J Mol Cell Cardiol 2016; 98: 62-72.
[http://dx.doi.org/10.1016/j.yjmcc.2016.06.007] [PMID: 27318036]
[49]
Oda T, Yang Y, Nitu FR, et al. In cardiomyocytes, binding of unzipping peptide activates ryanodine receptor 2 and reciprocally inhibits calmodulin binding. Circ Res 2013; 112(3): 487-97.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.300290] [PMID: 23233753]
[50]
Yang Y, Guo T, Oda T, et al. Cardiac myocyte Z-line calmodulin is mainly RyR2-bound, and reduction is arrhythmogenic and occurs in heart failure. Circ Res 2014; 114(2): 295-306.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.302857] [PMID: 24186966]
[51]
Rebbeck RT, Singh DP, Janicek KA, et al. RyR1-targeted drug discovery pipeline integrating FRET-based high-throughput screening and human myofiber dynamic Ca2+ assays. Sci Rep 2020; 10(1): 1791.
[http://dx.doi.org/10.1038/s41598-020-58461-1] [PMID: 32019969]
[52]
Murayama T, Kurebayashi N, Ishigami-Yuasa M, et al. Efficient high-throughput screening by endoplasmic reticulum Ca2+ measurement to identify inhibitors of ryanodine receptor Ca2+-release channels. Mol Pharmacol 2018; 94(1): 722-30.
[http://dx.doi.org/10.1124/mol.117.111468] [PMID: 29674523]
[53]
Wirth T, Parker N, Ylä-Herttuala S. History of gene therapy. Gene 2013; 525(2): 162-9.
[http://dx.doi.org/10.1016/j.gene.2013.03.137] [PMID: 23618815]
[54]
Al-Zaidy SA, Kolb SJ, Lowes L, et al. AVXS-101 (onasemnogene abeparvovec) for SMA1: Comparative study with a prospective natural history cohort. J Neuromuscul Dis 2019; 6(3): 307-17.
[http://dx.doi.org/10.3233/JND-190403] [PMID: 31381526]
[55]
Messina S, Sframeli M. New treatments in spinal muscular atrophy: Positive results and new challenges. J Clin Med 2020; 9(7): 2222.
[http://dx.doi.org/10.3390/jcm9072222] [PMID: 32668756]
[56]
Ross JA, Tasfaout H, Levy Y, et al. rAAV-related therapy fully rescues myonuclear and myofilament function in X-linked myotubular myopathy. Acta Neuropathol Commun 2020; 8(1): 167.
[http://dx.doi.org/10.1186/s40478-020-01048-8] [PMID: 33076971]
[57]
McGreevy JW, Hakim CH, McIntosh MA, Duan D. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy. Dis Model Mech 2015; 8(3): 195-213.
[http://dx.doi.org/10.1242/dmm.018424] [PMID: 25740330]
[58]
Kodippili K, Hakim CH, Pan X, et al. Dual AAV gene therapy for duchenne muscular dystrophy with a 7-kb mini-dystrophin gene in the canine model. Hum Gene Ther 2018; 29(3): 299-311.
[http://dx.doi.org/10.1089/hum.2017.095] [PMID: 28793798]
[59]
Fairclough RJ, Wood MJ, Davies KE. Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches. Nat Rev Genet 2013; 14(6): 373-8.
[http://dx.doi.org/10.1038/nrg3460] [PMID: 23609411]
[60]
Tinsley J, Deconinck N, Fisher R, et al. Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat Med 1998; 4(12): 1441-4.
[http://dx.doi.org/10.1038/4033] [PMID: 9846586]
[61]
Sengupta K, Mishra MK, Loro E, Spencer MJ, Pyle AD, Khurana TS. Genome editing-mediated utrophin upregulation in duchenne muscular dystrophy stem cells. Mol Ther Nucleic Acids 2020; 22: 500-9.
[http://dx.doi.org/10.1016/j.omtn.2020.08.031] [PMID: 33230452]
[62]
Sengupta K, Loro E, Khurana TS. PMO-based let-7c site blocking oligonucleotide (SBO) mediated utrophin upregulation in mdx mice, a therapeutic approach for Duchenne muscular dystrophy (DMD). Sci Rep 2020; 10(1): 21492.
[http://dx.doi.org/10.1038/s41598-020-76338-1] [PMID: 33298994]
[63]
Pisani C, Strimpakos G, Gabanella F, et al. Utrophin up-regulation by artificial transcription factors induces muscle rescue and impacts the neuromuscular junction in mdx mice. Biochim Biophys Acta Mol Basis Dis 2018; 1864(4 Pt A): 1172-82.
[http://dx.doi.org/10.1016/j.bbadis.2018.01.030] [PMID: 29408646]
[64]
Lanner JT, Georgiou DK, Joshi AD, Hamilton SL. Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2010; 2(11): a003996.
[http://dx.doi.org/10.1101/cshperspect.a003996] [PMID: 20961976]
[65]
Chiu W, Hsun Y-H, Chang K-J, et al. Current genetic survey and potential gene-targeting therapeutics for neuromuscular diseases. Int J Mol Sci 2020; 21(24): 9589.
[http://dx.doi.org/10.3390/ijms21249589] [PMID: 33339321]
[66]
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; 28(1): 4-15.
[http://dx.doi.org/10.1016/j.nmd.2017.10.004] [PMID: 29203355]
[67]
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): 1723-32.
[http://dx.doi.org/10.1056/NEJMoa1702752] [PMID: 29091570]
[68]
Gidaro T, Servais L. Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps. Dev Med Child Neurol 2019; 61(1): 19-24.
[http://dx.doi.org/10.1111/dmcn.14027] [PMID: 30221755]
[69]
Rendu J, Brocard J, Denarier E, et al. Exon skipping as a therapeutic strategy applied to an RYR1 mutation with pseudo-exon inclusion causing a severe core myopathy. Hum Gene Ther 2013; 24(7): 702-13.
[http://dx.doi.org/10.1089/hum.2013.052] [PMID: 23805838]
[70]
Loy RE, Lueck JD, Mostajo-Radji MA, Carrell EM, Dirksen RT. Allele-specific gene silencing in two mouse models of autosomal dominant skeletal myopathy. PLoS One 2012; 7(11): e49757.
[http://dx.doi.org/10.1371/journal.pone.0049757] [PMID: 23152933]
[71]
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337(6096): 816-21.
[http://dx.doi.org/10.1126/science.1225829] [PMID: 22745249]
[72]
Sharma G, Sharma AR, Bhattacharya M, Lee S-S, Chakraborty C. CRISPR-Cas9: A preclinical and clinical perspective for the treatment of human diseases. Mol Ther 2021; 29(2): 571-86.
[http://dx.doi.org/10.1016/j.ymthe.2020.09.028] [PMID: 33238136]
[73]
Strzyz P. CRISPR-Cas9 wins nobel. Nat Rev Mol Cell Biol 2020; 21(12): 714.
[http://dx.doi.org/10.1038/s41580-020-00307-9] [PMID: 33051620]
[74]
Chemello F, Bassel-Duby R, Olson EN. Correction of muscular dystrophies by CRISPR gene editing. J Clin Invest 2020; 130(6): 2766-76.
[http://dx.doi.org/10.1172/JCI136873] [PMID: 32478678]
[75]
Long C, Amoasii L, Mireault AA, et al. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 2016; 351(6271): 400-3.
[http://dx.doi.org/10.1126/science.aad5725] [PMID: 26721683]
[76]
Nelson CE, Hakim CH, Ousterout DG, et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 2016; 351(6271): 403-7.
[http://dx.doi.org/10.1126/science.aad5143] [PMID: 26721684]
[77]
Tabebordbar M, Zhu K, Cheng JKW, et al. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 2016; 351(6271): 407-11.
[http://dx.doi.org/10.1126/science.aad5177] [PMID: 26721686]
[78]
Amoasii L, Hildyard JCW, Li H, et al. Gene editing restores dystrophin expression in a canine model of duchenne muscular dystrophy. Science 2018; 362(6410): 86-91.
[http://dx.doi.org/10.1126/science.aau1549] [PMID: 30166439]
[79]
Moretti A, Fonteyne L, Giesert F, et al. Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of duchenne muscular dystrophy. Nat Med 2020; 26(2): 207-14.
[http://dx.doi.org/10.1038/s41591-019-0738-2] [PMID: 31988462]
[80]
Min Y-L, Li H, Rodriguez-Caycedo C, et al. CRISPR-Cas9 corrects duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells. Sci Adv 2019; 5(3): eaav4324.
[http://dx.doi.org/10.1126/sciadv.aav4324] [PMID: 30854433]
[81]
Nelson CE, Wu Y, Gemberling MP, et al. Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy. Nat Med 2019; 25(3): 427-32.
[http://dx.doi.org/10.1038/s41591-019-0344-3] [PMID: 30778238]
[82]
Marsh S, Hanson B, Wood MJA, Varela MA, Roberts TC. Application of CRISPR-Cas9-mediated genome editing for the treatment of myotonic dystrophy type 1. Mol Ther 2020; 28(12): 2527-39.
[http://dx.doi.org/10.1016/j.ymthe.2020.10.005] [PMID: 33171139]
[83]
Hacein-Bey-Abina S, Le Deist F, Carlier F, et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med 2002; 346(16): 1185-93.
[http://dx.doi.org/10.1056/NEJMoa012616] [PMID: 11961146]
[84]
Hanlon KS, Kleinstiver BP, Garcia SP, et al. High levels of AAV vector integration into CRISPR-induced DNA breaks. Nat Commun 2019; 10(1): 4439.
[http://dx.doi.org/10.1038/s41467-019-12449-2] [PMID: 31570731]
[85]
van Westering TLE, Lomonosova Y, Coenen-Stass AML, et al. Uniform sarcolemmal dystrophin expression is required to prevent extracellular microRNA release and improve dystrophic pathology. J Cachexia Sarcopenia Muscle 2020; 11(2): 578-93.
[http://dx.doi.org/10.1002/jcsm.12506] [PMID: 31849191]
[86]
Brokowski C, Adli M. CRISPR Ethics: Moral considerations for applications of a powerful tool. J Mol Biol 2019; 431(1): 88-101.
[http://dx.doi.org/10.1016/j.jmb.2018.05.044] [PMID: 29885329]
[87]
Doudna JA. The promise and challenge of therapeutic genome editing. Nature 2020; 578(7794): 229-36.
[http://dx.doi.org/10.1038/s41586-020-1978-5] [PMID: 32051598]