title: Zebrafish based small molecule screens for novel DMD drugs.
abstract: Recently, a number of chemical and drug screens using zebrafish embryos have been published. Using zebrafish dystrophin mutants, we screened a chemical library for small molecules that modulate the muscle phenotype and identified seven small molecules that influence muscle pathology in dystrophin-null zebrafish. One chemical, aminophylline, which is known to be a non-selective phosphodiesterase (PDE) inhibitor, had the greatest ability to restore normal muscle structure and to up-regulate cAMP-dependent protein kinase (PKA) in treated dystrophin deficient fish. Our methodologies, which combine drug screening with assessment of the chemical effects by genotyping and staining with anti-dystrophin, provide a powerful means to identify template structures potentially relevant to the development of novel human muscular dystrophies therapeutics.
authors: Division of Genetics, Program in Genomics, Children's Hospital Boston, Children's Hospital Boston, MA, USA ; Department of Genetics, Harvard Medical School, Children's Hospital Boston, MA, USA ; The Manton Center for Orphan Disease Research, Children's Hospital Boston, MA, USA.
authors: Genri
authors: G
authors: Kawahara
authors: Louis M
authors: LM
authors: Kunkel
references: Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R265-70
references: 14504264
references: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):12965-9
references: 11087852
references: Hum Mol Genet. 2011 May 1;20(9):1712-25
references: 21296866
references: Nat Med. 2003 Aug;9(8):1009-14
references: 12847521
references: Eur J Cardiothorac Surg. 2004 May;25(5):766-71
references: 15082280
references: Dev Dyn. 1995 Jul;203(3):253-310
references: 8589427
references: Nature. 2007 May 3;447(7140):87-91
references: 17450125
references: Nature. 2008 Nov 27;456(7221):511-5
references: 18953332
references: Hum Mol Genet. 2010 Feb 15;19(4):623-33
references: 19955119
references: PLoS One. 2007 Aug 29;2(8):e806
references: 17726536
references: Dev Biol. 2007 Sep 15;309(2):180-92
references: 17678642
references: EMBO J. 2006 May 17;25(10):2051-61
references: 16642035
references: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7092-7
references: 17438294
references: Hum Mol Genet. 2011 May 1;20(9):1763-75
references: 21317159
references: Lancet. 1994 Apr 23;343(8904):1006-8
references: 7909049
references: Exp Cell Res. 2005 Mar 10;304(1):105-15
references: 15707578
references: Nat Chem Biol. 2005 Dec;1(7):366-70
references: 16372403
references: Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5331-6
references: 21402949
references: Nat Rev Drug Discov. 2005 Jan;4(1):35-44
references: 15688071
references: Genomics. 2008 Sep;92(3):159-67
references: 18632251
references: Biochem Biophys Res Commun. 2011 Sep 23;413(2):358-63
references: 21893049
references: Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19079-83
references: 20956307
references: Hum Mol Genet. 2009 Jan 1;18(1):202-11
references: 18957474
references: Brain. 2008 Jun;131(Pt 6):1551-61
references: 18477595
references: Curr Opin Genet Dev. 2000 Jun;10(3):252-6
references: 10826982
references: Nat Biotechnol. 2003 Aug;21(8):879-83
references: 12894204
references: Hum Mol Genet. 2003 Mar 15;12(6):601-15
references: 12620966
references: Inflammation. 1998 Dec;22(6):545-57
references: 9824770
references: BMC Genomics. 2007 Mar 20;8:79
references: 17374169
references: Hum Mol Genet. 2010 Jun 15;19(12):2433-44
references: 20338942