Drug to Correct Premature "Stop” Mutations

These include cystic fibrosis, muscular dystrophy, and hemophilia. An experimental drug called PTC124 binds to a key component of the protein-making machinery, allowing it to read past the misplaced stop signal. Normal genes are not affected, since their stop codon is at the end of the messenger RNA strand rather than in the middle.

In the late 1900s, it was discovered that an antibiotic called gentamicin induces protein-making machinery to read through these stop signals. A trial has now shown that when gentamicin is applied to the nostrils of people with cystic fibrosis, normal CFTR (cystic fibrosis transmembrane regulator) protein production is restored. The results were reported in the October 9, 2003, issue of The New England Journal of Medicine.

However, gentamicin is absorbed badly by the body so it must be injected or inhaled, and can cause rare but serious side effects such as hearing loss and kidney damage. So PTC Therapeutics (Plainfield, NJ, USA) designed PTC124 to have similar properties but to be safer and more easily absorbed than gentamicin. In mice with muscular dystrophy, the drug restored expression of the dystophin protein found on the surface of muscle cells, while tests on mice with cystic fibrosis suggest that the drug restores production of functional CFTR.




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