@article{dc262d8865934c12a1accc1835bfdba2,
title = "SMRT compounds abrogate cellular phenotypes of ataxia telangiectasia in neural derivatives of patient-specific hiPSCs",
abstract = "Ataxia telangiectasia is a devastating neurodegenerative disease caused primarily by loss of function mutations in ATM, a hierarchical DNA repair gene and tumour suppressor. So far, murine models of ataxia telangiectasia have failed to accurately recapitulate many aspects of the disease, most notably, the progressive cerebellar ataxia. Here we present a model of human ataxia telangiectasia using induced pluripotent stem cells, and show that small molecule read-through compounds, designed to induce read-through of mRNA around premature termination codons, restore ATM activity and improve the response to DNA damage. This platform allows for efficient screening of novel compounds, identification of target and off-target effects, and preclinical testing on relevant cell types for the pathogenic dissection and treatment of ataxia telangiectasia.",
author = "Peiyee Lee and Martin, {Nathan T.} and Kotoka Nakamura and Soheila Azghadi and Mandana Amiri and Uri Ben-David and Susan Perlman and Gatti, {Richard A.} and Hailiang Hu and Lowry, {William E.}",
note = "Funding Information: P.L., N.T.M., K.N., S.A., M.A., U.B.-D. and H.H. performed and helped design experiments. P.L., N.T.M., R.A.G., H.H. and W.E.L. interpreted experiments and wrote the manuscript. For correspondence regarding small molecule compounds, contact H.H.; regarding cell culture or reprogramming, contact W.E.L., R.A.G. and W.E.L. provided financial support for the experiments. W.E.L. holds the Maria Rowena Ross Chair in Cell Biology. P.L. was funded by a training grant from CIRM (TG2-01169). R.A.G. holds the Rebecca Smith Chair in Molecular Pathology and Laboratory Medicine. This work was supported by grants from: CIRM no. RT2-01920, NIH R01NS052528, APRAT and A-T Ease Foundation to R.A.G.",
year = "2013",
doi = "10.1038/ncomms2824",
language = "אנגלית",
volume = "4",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}
