Ex vivo treatment with a novel synthetic aminoglycoside NB54 in primary fibroblasts from Rett syndrome patients suppresses MECP2 nonsense mutations

PLoS ONE

Volumn 6, Issue 6, 2011, Pages

  Vecsler, Manuela ^a,b   Ben Zeev, Bruria ^a   Nudelman, Igor ^c   Anikster, Yair ^a   Simon, Amos J ^a   Amariglio, Ninette ^a   Rechavi, Gideon ^a,b   Baasov, Timor ^c   Gak, Eva ^a,b  

^a SHEBA MEDICAL CENTER   (Israel)

^b TEL AVIV UNIVERSITY   (Israel)

^c TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE DERIVATIVE; BRAIN DERIVED NEUROTROPHIC FACTOR; GENTAMICIN; METHYL CPG BINDING PROTEIN 2; NB 54; UNCLASSIFIED DRUG; 5 O (5 AMINO 5 DEOXYRIBOFURANOSYL) 1N (4 AMINO 2 HYDROXYBUTANOYL)PAROMAMINE; 5-O-(5-AMINO-5-DEOXYRIBOFURANOSYL)-1N-(4-AMINO-2-HYDROXYBUTANOYL)PAROMAMINE; AMINOGLYCOSIDE; MECP2 PROTEIN, HUMAN; MESSENGER RNA;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL NUCLEUS; COMPARATIVE EFFECTIVENESS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; EX VIVO STUDY; FIBROBLAST; GENE LOCATION; GENE REPRESSION; GENE TRANSLOCATION; HUMAN; HUMAN CELL; NONSENSE MUTATION; RETT SYNDROME; CELL CULTURE; CELL DEATH; CELL STRAIN HEK293; GENE EXPRESSION REGULATION; GENETICS; MALE; METABOLISM; PATHOLOGY; STOP CODON;

AMINOGLYCOSIDES; BRAIN-DERIVED NEUROTROPHIC FACTOR; CELL DEATH; CELL NUCLEUS; CELLS, CULTURED; CODON, NONSENSE; FIBROBLASTS; GENE EXPRESSION REGULATION; GENTAMICINS; HEK293 CELLS; HUMANS; MALE; METHYL-CPG-BINDING PROTEIN 2; RETT SYNDROME; RNA, MESSENGER;

EID: 79958747922     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0020733     Document Type: Article

References (54)

1. Hagberg B, Hagberg G, (1997) Rett syndrome: epidemiology and geographical variability. Eur Child Adolesc Psychiatry 6 (Suppl 1): 5-7.
2. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, et al. (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23: 185-188.
3. Christodoulou J, Grimm A, Maher T, Bennetts B, (2003) RettBASE: The IRSA MECP2 variation database-a new mutation database in evolution. Hum Mutat 21: 466-472.
4. Lee SS, Wan M, Francke U, (2001) Spectrum of MECP2 mutations in Rett syndrome. Brain Dev 23 (Suppl 1): S138-143.
5. Trappe R, Laccone F, Cobilanschi J, Meins M, Huppke P, et al. (2001) MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am J Hum Genet 68: 1093-1101.
6. Amir RE, Van den Veyver IB, Schultz R, Malicki DM, Tran CQ, et al. (2000) Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes. Ann Neurol 47: 670-679.
7. Meins M, Lehmann J, Gerresheim F, Herchenbach J, Hagedorn M, et al. (2005) Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome. J Med Genet 42: e12.
8. Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, et al. (2005) Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 77: 442-453.
9. Kriaucionis S, Bird A, (2004) The major form of MeCP2 has a novel N-terminus generated by alternative splicing. Nucleic Acids Res 32: 1818-1823.
10. Mnatzakanian GN, Lohi H, Munteanu I, Alfred SE, Yamada T, et al. (2004) A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat Genet 36: 339-341.
11. Nan X, Tate P, Li E, Bird A, (1996) DNA methylation specifies chromosomal localization of MeCP2. Mol Cell Biol 16: 414-421.
12. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, et al. (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19: 187-191.
13. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, et al. (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393: 386-389.
14. Chen WG, Chang Q, Lin Y, Meissner A, West AE, et al. (2003) Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302: 885-889.
15. Martinowich K, Hattori D, Wu H, Fouse S, He F, et al. (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302: 890-893.
16. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, et al. (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320: 1224-1229.
17. Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, et al. (2005) Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci U S A 102: 17551-17558.
18. Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, et al. (2010) Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell 37: 457-468.
19. Chen RZ, Akbarian S, Tudor M, Jaenisch R, (2001) Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet 27: 327-331.
20. Guy J, Hendrich B, Holmes M, Martin JE, Bird A, (2001) A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27: 322-326.
21. Giacometti E, Luikenhuis S, Beard C, Jaenisch R, (2007) Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci U S A 104: 1931-1936.
22. Guy J, Gan J, Selfridge J, Cobb S, Bird A, (2007) Reversal of neurological defects in a mouse model of Rett syndrome. Science 315: 1143-1147.
23. Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, et al. (2004) Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13: 2679-2689.
24. Laccone F, Huppke P, Hanefeld F, Meins M, (2001) Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions. Hum Mutat 17: 183-190.
25. Burke JF, Mogg AE, (1985) Suppression of a nonsense mutation in mammalian cells in vivo by the aminoglycoside antibiotics G-418 and paromomycin. Nucleic Acids Res 13: 6265-6272.
26. Kaufman RJ, (1999) Correction of genetic disease by making sense from nonsense. J Clin Invest 104: 367-368.
27. Manuvakhova M, Keeling K, Bedwell DM, (2000) Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system. RNA 6: 1044-1055.
28. Barton-Davis ER, Cordier L, Shoturma DI, Leland SE, Sweeney HL, (1999) Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J Clin Invest 104: 375-381.
29. Du M, Jones JR, Lanier J, Keeling KM, Lindsey JR, et al. (2002) Aminoglycoside suppression of a premature stop mutation in a Cftr-/- mouse carrying a human CFTR-G542X transgene. J Mol Med 80: 595-604.
30. Kerem E, (2004) Pharmacologic therapy for stop mutations: how much CFTR activity is enough? Curr Opin Pulm Med 10: 547-552.
31. Brendel C, Klahold E, Gartner J, Huppke P, (2009) Suppression of nonsense mutations in Rett syndrome by aminoglycoside antibiotics. Pediatr Res 65: 520-523.
32. Keeling KM, Bedwell DM, (2005) Pharmacological Suppression of Premature Stop Mutations that Cause Genetic Diseases. Current Pharmacogenomics 3: 259-269.
33. Hainrichson M, Nudelman I, Baasov T, (2008) Designer aminoglycosides: the race to develop improved antibiotics and compounds for the treatment of human genetic diseases. Org Biomol Chem 6: 227-239.
34. Goldmann T, Rebibo-Sabbah A, Overlack N, Nudelman I, Belakhov V, et al. (2010) Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina. Invest Ophthalmol Vis Sci 51: 6671-6680.
35. Nudelman I, Rebibo-Sabbah A, Cherniavsky M, Belakhov V, Hainrichson M, et al. (2009) Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations. J Med Chem 52: 2836-2845.
36. Politano L, Nigro G, Nigro V, Piluso G, Papparella S, et al. (2003) Gentamicin administration in Duchenne patients with premature stop codon. Preliminary results. Acta Myol 22: 15-21.
37. Wagner KR, Hamed S, Hadley DW, Gropman AL, Burstein AH, et al. (2001) Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations. Ann Neurol 49: 706-711.
38. Ramalho AS, Beck S, Meyer M, Penque D, Cutting GR, et al. (2002) Five percent of normal cystic fibrosis transmembrane conductance regulator mRNA ameliorates the severity of pulmonary disease in cystic fibrosis. Am J Respir Cell Mol Biol 27: 619-627.
39. Popescu AC, Sidorova E, Zhang G, Eubanks JH, (2010) Aminoglycoside-mediated partial suppression of MECP2 nonsense mutations responsible for Rett syndrome in vitro. J Neurosci Res 88: 2316-2324.
40. Howard MT, Shirts BH, Petros LM, Flanigan KM, Gesteland RF, et al. (2000) Sequence specificity of aminoglycoside-induced stop condon readthrough: potential implications for treatment of Duchenne muscular dystrophy. Ann Neurol 48: 164-169.
41. Brendel C, Belakhov V, Werner H, Wegener E, Gartner J, et al. (2011) Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model. J Mol Med 89: 389-398.
42. Vecsler M, Simon AJ, Amariglio N, Rechavi G, Gak E, (2010) MeCP2 deficiency downregulates specific nuclear proteins that could be partially recovered by valproic acid in vitro. Epigenetics 5: 61-67.
43. Bidou L, Hatin I, Perez N, Allamand V, Panthier JJ, et al. (2004) Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment. Gene Ther 11: 619-627.
44. Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W, et al. (2010) Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann Neurol 67: 771-780.
45. Culbertson MR, (1999) RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer. Trends Genet 15: 74-80.
46. Hermann T, (2007) Aminoglycoside antibiotics: old drugs and new therapeutic approaches. Cell Mol Life Sci 64: 1841-1852.
47. Petel-Galil Y, Ben-Zeev B, Greenbaum I, Vecsler M, Goldman B, et al. (2007) Comprehensive diagnosis of Rett's syndrome relying on genetic, epigenetic and expression evidence of deficiency of the methyl-CpG-binding protein 2 gene: study of a cohort of Israeli patients. J Med Genet 44: e56.
48. Linde L, Boelz S, Nissim-Rafinia M, Oren YS, Wilschanski M, et al. (2007) Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. J Clin Invest 117: 683-692.
49. Traynor J, Agarwal P, Lazzeroni L, Francke U, (2002) Gene expression patterns vary in clonal cell cultures from Rett syndrome females with eight different MECP2 mutations. BMC Med Genet 3: 12.
50. Huang ZJ, Kirkwood A, Pizzorusso T, Porciatti V, Morales B, et al. (1999) BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98: 739-755.
51. Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, et al. (2004) Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A 101: 10827-10832.
52. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R, (2006) The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49: 341-348.
53. Kline DD, Ogier M, Kunze DL, Katz DM, (2010) Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in Mecp2-null mice. J Neurosci 30: 5303-5310.
54. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, et al. (2007) PTC124 targets genetic disorders caused by nonsense mutations. Nature 447: 87-91.