A new series of small molecular weight compounds induce read through of all three types of nonsense mutations in the ATM gene

Molecular Therapy

Volumn 21, Issue 9, 2013, Pages 1653-1660

  Du, Liutao ^a   Jung, Michael E ^b   Damoiseaux, Robert ^b   Completo, Gladys ^b   Fike, Francesca ^a   Ku, Jin Mo ^b   Nahas, Shareef ^a   Piao, Cijing ^a   Hu, Hailiang ^a   Gatti, Richard A ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATALUREN; ATM PROTEIN; GJ 071; GJ 072; GJ 103; GJ 104; GJ 105; GJ 106; GJ 109; GJ 111; GJ 112; GJ 113; MOLECULAR THERAPY AGENT; READ THROUGH COMPOUND; RTC 13; RTC 204; RTC 219; UNCLASSIFIED DRUG;

ARTICLE; ATAXIA TELANGIECTASIA; ATM GENE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG MECHANISM; DRUG RESEARCH; DRUG STRUCTURE; DRUG TOLERABILITY; ENZYME LINKED IMMUNOSORBENT ASSAY; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; MOLECULAR WEIGHT; NONSENSE MUTATION; STOP CODON; STRUCTURE ACTIVITY RELATION;

ATAXIA TELANGIECTASIA;

ACETANILIDES; ATAXIA TELANGIECTASIA; ATAXIA TELANGIECTASIA MUTATED PROTEINS; BENZODIOXOLES; CELLS, CULTURED; CODON, NONSENSE; CODON, TERMINATOR; DNA-BINDING PROTEINS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MOLECULAR TARGETED THERAPY; MOLECULAR WEIGHT; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; THIOUREA; TRIAZOLES;

EID: 84883742368     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2013.150     Document Type: Article

References (43)

1. Mendell, JT and Dietz, HC (2001). When the message goes awry: disease-producing mutations that influence mRNA content and performance. Cell 107: 411-414. (Pubitemid 33152776)
2. Howard, MT, Shirts, BH, Petros, LM, Flanigan, KM, Gesteland, RF and Atkins, JF (2000). Sequence specificity of aminoglycoside-induced stop condon readthrough: potential implications for treatment of Duchenne muscular dystrophy. Ann Neurol 48: 164-169. (Pubitemid 30617034)
3. Du, M, Keeling, KM, Fan, L, Liu, X and Bedwell, DM (2009). Poly-L-aspartic acid enhances and prolongs gentamicin-mediated suppression of the CFTR-G542X mutation in a cystic fibrosis mouse model. J Biol Chem 284: 6885-6892.
4. Zingman, LV, Park, S, Olson, TM, Alekseev, AE and Terzic, A (2007). Aminoglycosideinduced translational read-through in disease: overcoming nonsense mutations by pharmacogenetic therapy. Clin Pharmacol Ther 81: 99-103. (Pubitemid 46050873)
5. Keeling, KM and Bedwell, DM (2011). Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases. Wiley Interdiscip Rev RNA 2: 837-852.
6. Du, L, Damoiseaux, R, Nahas, S, Gao, K, Hu, H, Pollard, JM et al. (2009). Nonaminoglycoside compounds induce readthrough of nonsense mutations. J Exp Med 206: 2285-2297.
7. Du, L, Kayali, R, Bertoni, C, Fike, F, Hu, H, Iversen, PL et al. (2011). Arginine-rich cell-penetrating peptide dramatically enhances AMO-mediated ATM aberrant splicing correction and enables delivery to brain and cerebellum. Hum Mol Genet 20: 3151-3160.
8. Ramalho, AS, Beck, S, Meyer, M, Penque, D, Cutting, GR and Amaral, MD (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. (Pubitemid 35301816)
9. Gilad, S, Bar-Shira, A, Harnik, R, Shkedy, D, Ziv, Y, Khosravi, R et al. (1996). Ataxia-telangiectasia: founder effect among north African Jews. Hum Mol Genet 5: 2033-2037. (Pubitemid 26413651)
10. Kerem, E (2004). Pharmacologic therapy for stop mutations: how much CFTR activity is enough? Curr Opin Pulm Med 10: 547-552. (Pubitemid 39441452)
11. Chun, HH and Gatti, RA (2004). Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst) 3: 1187-1196. (Pubitemid 38997962)
12. Kayali, R, Ku, JM, Khitrov, G, Jung, ME, Prikhodko, O and Bertoni, C (2012). Readthrough compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy. Hum Mol Genet 21: 4007-4020.
13. Du, M, Liu, X, Welch, EM, Hirawat, S, Peltz, SW and Bedwell, DM (2008). PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc Natl Acad Sci USA 105: 2064-2069. (Pubitemid 351439465)
14. Bedwell, DM, Kaenjak, A, Benos, DJ, Bebok, Z, Bubien, JK, Hong, J et al. (1997). Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat Med 3: 1280-1284. (Pubitemid 27508832)
15. Howard, M, Frizzell, RA and Bedwell, DM (1996). Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat Med 2: 467-469. (Pubitemid 26191920)
16. Loufrani, L, Dubroca, C, You, D, Li, Z, Levy, B, Paulin, D et al. (2004). Absence of dystrophin in mice reduces NO-dependent vascular function and vascular density: total recovery after a treatment with the aminoglycoside gentamicin. Arterioscler Thromb Vasc Biol 24: 671-676. (Pubitemid 38451602)
17. Keeling, KM, Brooks, DA, Hopwood, JJ, Li, P, Thompson, JN and Bedwell, DM (2001). Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation. Hum Mol Genet 10: 291-299. (Pubitemid 32123987)
18. Sossi, V, Giuli, A, Vitali, T, Tiziano, F, Mirabella, M, Antonelli, A et al. (2001). Premature termination mutations in exon 3 of the SMN1 gene are associated with exon skipping and a relatively mild SMA phenotype. Eur J Hum Genet 9: 113-120. (Pubitemid 32156692)
19. Lai, CH, Chun, HH, Nahas, SA, Mitui, M, Gamo, KM, Du, L et al. (2004). Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci USA 101: 15676-15681. (Pubitemid 39473547)
20. Politano, L, Nigro, G, Nigro, V, Piluso, G, Papparella, S, Paciello, O et al. (2003). Gentamicin administration in Duchenne patients with premature stop codon. Preliminary results. Acta Myol 22: 15-21. (Pubitemid 36966404)
21. Wilschanski, M, Famini, C, Blau, H, Rivlin, J, Augarten, A, Avital, A et al. (2000). A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations. Am J Respir Crit Care Med 161(3 Pt 1): 860-865. (Pubitemid 30171743)
22. Clancy, JP, Bebök, Z, Ruiz, F, King, C, Jones, J, Walker, L et al. (2001). Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis. Am J Respir Crit Care Med 163: 1683-1692. (Pubitemid 32578776)
23. Mingeot-Leclercq, MP and Tulkens, PM (1999). Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 43: 1003-1012. (Pubitemid 29214718)
24. Guan, MX, Fischel-Ghodsian, N and Attardi, G (2000). A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity. Hum Mol Genet 9: 1787-1793. (Pubitemid 30608612)
25. Zilberberg, A, Lahav, L and Rosin-Arbesfeld, R (2010). Restoration of APC gene function in colorectal cancer cells by aminoglycoside-and macrolide-induced readthrough of premature termination codons. Gut 59: 496-507.
26. Welch, EM, Barton, ER, Zhuo, J, Tomizawa, Y, Friesen, WJ, Trifillis, P et al. (2007). PTC124 targets genetic disorders caused by nonsense mutations. Nature 447: 87-91. (Pubitemid 46685839)
27. Hirawat, S, Welch, EM, Elfring, GL, Northcutt, VJ, Paushkin, S, Hwang, S et al. (2007). Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single-and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol 47: 430-444. (Pubitemid 46465953)
28. Guglieri, M and Bushby, K (2010). Molecular treatments in Duchenne muscular dystrophy. Curr Opin Pharmacol 10: 331-337.
29. Jung, ME, Ku, JM, Du, L, Hu, H and Gatti, RA (2011). Synthesis and evaluation of compounds that induce readthrough of premature termination codons. Bioorg Med Chem Lett 21: 5842-5848.
30. Sun, X, Becker-Catania, SG, Chun, HH, Hwang, MJ, Huo, Y, Wang, Z et al. (2002). Early diagnosis of ataxia-telangiectasia using radiosensitivity testing. J Pediatr 140: 724-731. (Pubitemid 34666692)
31. Rowe, SM and Clancy, JP (2009). Pharmaceuticals targeting nonsense mutations in genetic diseases: progress in development. BioDrugs 23: 165-174.
32. Gatti, RA (2012). SMRT compounds correct nonsense mutations in primary immunodeficiency and other genetic models. Ann N Y Acad Sci 1250: 33-40.
33. Wilkinson, MF and Shyu, AB (2002). RNA surveillance by nuclear scanning? Nat Cell Biol 4: E144-E147. (Pubitemid 34746150)
34. Holbrook, JA, Neu-Yilik, G, Hentze, MW and Kulozik, AE (2004). Nonsense-mediated decay approaches the clinic. Nat Genet 36: 801-808. (Pubitemid 39014096)
35. Linde, L, Boelz, S, Nissim-Rafinia, M, Oren, YS, Wilschanski, M, Yaacov, Y 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. (Pubitemid 46348526)
36. Lee, Y and McKinnon, PJ (2000). ATM dependent apoptosis in the nervous system. Apoptosis 5: 523-529. (Pubitemid 32182550)
37. Gatti, RA and Vinters, HV (1985). Cerebellar pathology in ataxia-telangiectasia: the significance of basket cells. Kroc Found Ser 19: 225-232.
38. Vinters, HV, Gatti, RA and Rakic, P (1985). Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia-telangiectasia. Kroc Found Ser 19: 233-255.
39. Lee, P, Martin, NT, Nakamura, K, Azghadi, S, Amiri, M, Ben-David, U et al. (2013). SMRT compounds abrogate cellular phenotypes of ataxia telangiectasia in neural derivatives of patient-specific hiPSCs. Nat Commun 4: 1824.
40. Du, L, Lai, CH, Concannon, P and Gatti, RA (2008). Rapid screen for truncating ATM mutations by PTT-ELISA. Mutat Res 640: 139-144.
41. Nahas, SA, Butch, AW, Du, L and Gatti, RA (2009). Rapid flow cytometry-based structural maintenance of chromosomes 1 (SMC1) phosphorylation assay for identification of ataxia-telangiectasia homozygotes and heterozygotes. Clin Chem 55: 463-472.
42. Du, L, Pollard, JM and Gatti, RA (2007). Correction of prototypic ATM splicing mutations and aberrant ATM function with antisense morpholino oligonucleotides. Proc Natl Acad Sci USA 104: 6007-6012. (Pubitemid 47175649)
43. Huo, YK, Wang, Z, Hong, JH, Chessa, L, McBride, WH, Perlman, SL et al. (1994). Radiosensitivity of ataxia-telangiectasia, X-linked agammaglobulinemia, and related syndromes using a modified colony survival assay. Cancer Res 54: 2544-2547. (Pubitemid 24173733)