Editor's Summary
3 May 2007
PTC124: a no-nonsense drug
Many inherited diseases result from premature termination during translation of a messenger RNA into protein; one such disease is muscular dystrophy. Welch et al. now report that a small molecule, PTC124, enables the translation machinery to bypass sites that cause premature termination, but still terminate normally at the end of the mRNA. In human and mouse cells, this drug restores normal translation of the gene that is mutated in muscular dystrophy, and it restores muscle function in the mdx mouse model for the human disease. This work offers the hope that similar drugs might be used to target nonsense mutations and restore protein function in a wide variety of diseases. PTC124 is now undergoing clinical trials in muscular dystrophy and cystic fibrosis patients.
News and Views: Chemical Biology: Ignore the nonsense
A small molecule forces the protein-translation machinery to overlook the signals that would otherwise result in its premature termination. Genuine stop signs are, however, read and obeyed.
Anton Schmitz & Michael Famulok
doi:10.1038/nature05715
Letter: PTC124 targets genetic disorders caused by nonsense mutations
Ellen M. Welch, Elisabeth R. Barton, Jin Zhuo, Yuki Tomizawa, Westley J. Friesen, Panayiota Trifillis, Sergey Paushkin, Meenal Patel, Christopher R. Trotta, Seongwoo Hwang, Richard G. Wilde, Gary Karp, James Takasugi, Guangming Chen, Stephen Jones, Hongyu Ren, Young-Choon Moon, Donald Corson, Anthony A. Turpoff, Jeffrey A. Campbell, M. Morgan Conn, Atiyya Khan, Neil G. Almstead, Jean Hedrick, Anna Mollin, Nicole Risher, Marla Weetall, Shirley Yeh, Arthur A. Branstrom, Joseph M. Colacino, John Babiak, William D. Ju, Samit Hirawat, Valerie J. Northcutt, Langdon L. Miller, Phyllis Spatrick, Feng He, Masataka Kawana, Huisheng Feng, Allan Jacobson, Stuart W. Peltz & H. Lee Sweeney
doi:10.1038/nature05756
First paragraph | Full Text | PDF (579K) | Supplementary information
