Gene Therapy Options as New Treatment for Inherited Peripheral Neuropathy

다국어 초록 (Multilingual Abstract)

Inherited peripheral neuropathy (IPN) is caused by heterogeneous genetic mutations in more than 100 genes. So far, several treatment options for IPN have been developed and clinically evaluated using small molecules. However, gene therapy-based therapeutic strategies have not been aggressively investigated, likely due to the complexities of inheritance in IPN. Indeed, because the majority of the causative mutations of IPN lead to gainof- function rather than loss-of-function, developing a therapeutic strategy is more difficult, especially considering gene therapy for genetic diseases began with the simple idea of replacing a defective gene with a functional copy. Recent advances in gene manipulation technology have brought novel approaches to gene therapy and its clinical application for IPN treatment. For example, in addition to the classically used gene replacement for mutant genes in recessively inherited IPN, other techniques including gene addition to modify the disease phenotype, modulations of target gene expression, and techniques to edit mutant genes have been developed and evaluated as potent therapeutic strategies for dominantly inherited IPN. In this review, the current status of gene therapy for IPN and future perspectives will be discussed.

참고문헌 (Reference)

1 이지수, "miR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22" 한국뇌신경과학회 28 (28): 279-288, 2019

2 David RM, "Viral vectors : the road to reducing genotoxicity" 155 : 315-325, 2017

3 Sahenk Z, "TrkB and TrkC agonist antibodies improve function, electrophysiologic and pathologic features in Trembler J mice" 224 : 495-506, 2010

4 Suter U, "Trembler mouse carries a point mutation in a myelin gene" 356 : 241-244, 1992

5 Finkel RS, "Treatment of infantileonset spinal muscular atrophy with nusinersen : a phase 2, open-label, dose-escalation study" 388 : 3017-3026, 2016

6 Sereda MW, "Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease(CMT-1A)" 9 : 1533-1537, 2003

7 Emery DW, "The use of chromatin insulators to improve the expression and safety of integrating gene transfer vectors" 22 : 761-774, 2011

8 Valentijn LJ, "The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A" 1 : 166-170, 1992

9 Patel PI, "The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A" 1 : 159-165, 1992

10 Lee JS, "Targeted PMP22 TATA-box editing by CRISPR/Cas9 reduces demyelinating neuropathy of Charcot-Marie-Tooth disease type 1A in mice" 48 : 130-140, 2020

11 Wang D, "State-of-the-art human gene therapy:part II. Gene therapy strategies and clinical applications" 18 : 151-161, 2014

12 Fellmann C, "Stable RNA interference rules for silencing" 16 : 10-18, 2014

13 Fledrich R, "Soluble neuregulin-1modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A" 20 : 1055-1061, 2014

14 Nóbrega C, "Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice" 8 : e52396-, 2013

15 Moore CB, "Short hairpin RNA (shRNA): design, delivery, and assessment of gene knockdown" 629 : 141-158, 2010

16 Homs J, "Schwann cell targeting via intrasciatic injection of AAV8 as gene therapy strategy for peripheral nerve regeneration" 18 : 622-630, 2011

17 Chi X, "Safety of antisense oligonucleotide and siRNA-based therapeutics" 22 : 823-833, 2017

18 Zhou Y, "Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-Tooth type 2A model" 130 : 1756-1771, 2019

19 Pantera H, "Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer" 27 : 2830-2839, 2018

20 Verrier JD, "Reduction of Dicer impairs Schwann cell differentiation and myelination" 88 : 2558-2568, 2010

21 Bennett CF, "RNA targeting therapeutics : molecular mechanisms of antisense oligonucleotides as a therapeutic platform" 50 : 259-293, 2010

22 Nuzzo S, "Potential and challenges of aptamers as specific carriers of therapeutic oligonucleotides for precision medicine in cancer" 11 : E1521-, 2019

23 Carroll JB, "Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin" 19 : 2178-2185, 2011

24 Chumakov I, "Polytherapy with a combination of three repurposed drugs(PXT3003)down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy" 9 : 201-, 2014

25 Lee JS, "Pmp22 mutant allele-specific siRNA alleviates demyelinating neuropathic phenotype in vivo" 100 : 99-107, 2017

26 Rangaraju S, "Pharmacological induction of the heat shock response improves myelination in a neuropathic model" 32 : 105-115, 2008

27 Verrier JD, "Peripheral myelin protein 22 is regulated posttranscriptionally by miRNA-29a" 57 : 1265-1279, 2009

28 Colby J, "PMP22 carrying the trembler or trembler-J mutation is intracellularly retained in myelinating Schwann cells" 7 (7): 561-573, 2000

29 Zhao HT, "PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models" 128 : 359-368, 2018

30 Mercuri E, "Nusinersen versus Sham control in later-onset spinal muscular atrophy" 378 : 625-635, 2018

31 Takahashi M, "Normalization of overexpressed α-synuclein causing Parkinson's disease by a moderate gene silencing with RNA interference" 4 : e241-, 2015

32 Wu P, "Non-viral gene delivery systems for tissue repair and regeneration" 16 : 29-, 2018

33 Pipis M, "Nextgeneration sequencing in Charcot-Marie-Tooth disease : opportunities and challenges" 15 : 644-656, 2019

34 Pareyson D, "New developments in Charcot-Marie-Tooth neuropathy and related diseases" 30 : 471-480, 2017

35 Huang EJ, "Neurotrophins : roles in neuronal development and function" 24 : 677-736, 2001

36 Belin S, "Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy" 28 : 1260-1273, 2019

37 Sahenk Z, "NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients" 65 : 681-689, 2005

38 Senderek J, "Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy" 73 : 1106-1119, 2003

39 Bergamin G, "Mutation analysis of MFN2, GJB1, MPZ and PMP22 in Italian patients with axonal Charcot-Marie-Tooth disease" 16 : 540-550, 2014

40 Bartel DP, "MicroRNAs : genomics, biogenesis, mechanism, and function" 116 : 281-297, 2004

41 Yun B, "MicroRNA-deficient Schwann cells display congenital hypomyelination" 30 : 7722-7728, 2010

42 Rocha AG, "MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A" 360 : 336-341, 2018

43 Kagiava A, "Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy" 113 : E2421-E2429, 2016

44 Sargiannidou I, "Intraneural GJB1gene delivery improves nerve pathology in a model of Xlinked Charcot-Marie-Tooth disease" 78 : 303-316, 2015

45 Niederer HA, "Integration site and clonal expansion in human chronic retroviral infection and gene therapy" 6 : 4140-4164, 2014

46 Klein CJ, "Inherited neuropathies : clinical overview and update" 48 : 604-622, 2013

47 Jang SW, "Identification of drug modulators targeting genedosage disease CMT1A" 7 : 1205-1213, 2012

48 Lewis RA, "High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A : results of a randomized, double-masked, controlled trial" 70 : 981-987, 2013

49 Eggermann K, "Hereditary neuropathies" 115 : 91-97, 2018

50 Kim JY, "HDAC6inhibitors rescued the defective axonal mitochondrial movement in motor neurons derived from the induced pluripotent stem cells of peripheral neuropathy patients with HSPB1 mutation" 2016 : 9475981-, 2016

51 Benoy V, "HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease" 141 : 673-687, 2018

52 d'Ydewalle C, "HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease" 17 : 968-974, 2011

53 Harding AE, "Genetic aspects of hereditary motor and sensory neuropathy(types I and II)" 17 : 329-336, 1980

54 McManus MT, "Gene silencing in mammals by small interfering RNAs" 3 : 737-747, 2002

55 Schiza N, "Gene replacement therapy in a model of Charcot-Marie-Tooth 4C neuropathy" 142 : 1227-1241, 2019

56 Kagiava A, "Gene replacement therapy after neuropathy onset provides therapeutic benefit in a model of CMT1X" 28 : 3528-3542, 2019

57 Hoyng SA, "Gene delivery to rat and human Schwann cells and nerve segments : a comparison of AAV 1-9 and lentiviral vectors" 22 : 767-780, 2015

58 Cirak S, "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" 378 : 595-605, 2011

59 Hu Q, "Enzyme-responsive nanomaterials for controlled drug delivery" 6 : 12273-12286, 2014

60 Zhang JY, "Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents" 12 : 4171-4180, 2000

61 Prukop T, "Early short-term PXT3003 combinational therapy delays disease onset in a transgenic rat model of Charcot-Marie-Tooth disease 1A(CMT1A)" 14 : e0209752-, 2019

62 Pereira JA, "Dicer in Schwann cells is required for myelination and axonal integrity" 30 : 6763-6775, 2010

63 Woolley AG, "Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins, a reduced extent of myelination and increased apoptosis of Schwann cells" 56 : 306-317, 2008

64 Benoy V, "Development of improved HDAC6 inhibitors as pharmacological therapy for axonal Charcot-Marie-Tooth disease" 14 : 417-428, 2017

65 Meier C, "Developing Schwann cells acquire the ability to survive without axons by establishing an autocrine circuit involving insulin-like growth factor, neurotrophin-3, and platelet-derived growth factor-BB" 19 : 3847-3859, 1999

66 Lai WF, "Design of polymeric gene carriers for effective intracellular delivery" 36 : 713-728, 2018

67 Lupski JR, "DNA duplication associated with Charcot-Marie-Tooth disease type 1A" 66 : 219-232, 1991

68 Khajavi M, "Curcumin treatment abrogates endoplasmic reticulum retention and aggregation-induced apoptosis associated with neuropathy-causing myelin protein zerotruncating mutants" 77 : 841-850, 2005

69 Huxley C, "Correlation between varying levels of PMP22 expression and the degree of demyelination and reduction in nerve conduction velocity in transgenic mice" 7 : 449-458, 1998

70 Huxley C, "Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA" 5 : 563-569, 1996

71 Scherer SS, "Connexin32 is a myelin-related protein in the PNS and CNS" 15 : 8281-8294, 1995

72 Bergoffen J, "Connexin mutations in X-linked Charcot-Marie-Tooth disease" 262 : 2039-2042, 1993

73 Takahashi R, "Coenzyme Q10 therapy in hereditary motor sensory neuropathy type VI with novel mitofusin 2 mutation" 51 : 791-793, 2012

74 Piguet F, "Clinical gene therapy for neurodegenerative diseases : past, present, and future" 28 : 988-1003, 2017

75 Hong YB, "Clinical characterization and genetic analysis of Korean patients with X-linked Charcot-Marie-Tooth disease type 1" 22 : 172-181, 2017

76 Saporta AS, "Charcot-Marie-Tooth disease subtypes and genetic testing strategies" 69 : 22-33, 2011

77 Murphy SM, "Charcot-Marie-Tooth disease : frequency of genetic subtypes and guidelines for genetic testing" 83 : 706-710, 2012

78 Mali P, "Cas9 as a versatile tool for engineering biology" 10 : 957-963, 2013

79 Zhang F, "CRISPR/Cas9 for genome editing:progress, implications and challenges" 23 : R40-R46, 2014

80 Molla KA, "CRISPR/Cas-mediated base editing : technical considerations and practical applications" 37 : 1121-1142, 2019

81 Chittoor VG, "Biochemical characterization of protein quality control mechanisms during disease progression in the C22 mouse model of CMT1A" 5 : e00128-, 2013

82 Passage E, "Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease" 10 : 396-401, 2004

83 Pareyson D, "Ascorbic acid in Charcot-Marie-Tooth disease type 1A(CMT-TRIAAL and CMT-TRAUK) : a double-blind randomised trial" 10 : 320-328, 2011

84 Burns J, "Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children : a randomised, doubleblind, placebo-controlled, safety and efficacy trial" 8 : 537-544, 2009

85 Rigo F, "Antisensebased therapy for the treatment of spinal muscular atrophy" 199 : 21-25, 2012

86 Mann CJ, "Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse" 98 : 42-47, 2001

87 Meyer zu Horste G, "Antiprogesterone therapy uncouples axonal loss from demyelination in a transgenic rat model of CMT1A neuropathy" 61 : 61-72, 2007

88 Attarian S, "An exploratory randomised doubleblind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol(PXT3003)in patients with Charcot-Marie-Tooth disease type 1A" 9 : 199-, 2014

89 Feng X, "Allele-specific silencing of Alzheimer's disease genes : the amyloid precursor protein genes with Swedish or London mutations" 371 : 68-74, 2006

90 Xia X, "Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo" 23 : 578-586, 2006

91 Bremer J, "Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination" 5 (5): e12450-, 2010

92 Sahenk Z, "AAV1.NT-3 gene therapy for Charcot-Marie-Tooth neuropathy" 22 : 511-521, 2014

93 Monani UR, "A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2" 8 : 1177-1183, 1999

94 Zhong G, "A reversible RNA onswitch that controls gene expression of AAV-delivered therapeutics in vivo" 38 : 169-175, 2020