New Drug Potentially Effective Against Many Inherited Diseases

The drug, PTC124, had already been shown to be effective in treating mice with Duchenne muscular dystrophy, and is being touted as a possible therapeutic agent for the treatment of more than 2,400 inherited diseases caused by nonsense mutations.

Investigators at the University of Alabama (Birmingham, USA) worked with a line of genetically engineered mice that expressed a human CFTR-G542X transgene. The G542X gene carried a nonsense mutation that caused the mice to develop symptoms of cystic fibrosis.

Treatment of the animals with PTC124 suppressed the G542X nonsense mutation and restored a significant amount of human CFTR protein and function. These findings, reported in the February 6, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS), were confirmed by immunofluorescence staining. Furthermore, functional assays demonstrated that PTC124 treatment restored 24–29% of the average cAMP-stimulated transepithelial chloride currents observed in wild-type mice. These results indicated that PTC124 could effectively suppress the human CFTR-G542X nonsense mutation in vivo.

"Our study shows strong pre-clinical evidence that PTC124 is capable of suppressing nonsense mutations that cause cystic fibrosis,” said senior author Dr. David Bedwell, professor of microbiology at the University of Alabama. "We think this provides strong evidence for clinical trials with PTC124 in CF patients with this kind of mutation.”


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