PTC Therapeutics, a biopharmaceutical company based in South Plainfield, NJ, recently reported preclinical data suggesting that an investigational new drug called PTC124 may be able to bypass a genetic mutation responsible for a number of disorders. PTC124 targets so-called “nonsense mutations,” which interrupt the genetic directives essential for the production of several proteins. The interruption of a protein’s primary function can be the cause of many genetic disorders, such Duchenne muscular dystrophy (DMD), a muscle-wasting disease and cystic fibrosis.
The theoretical advantage of PTC124 lies in its potential as a therapy for a wide range of genetic disorders caused by nonsense mutations. According to PTC Therapeutics, besides DMD and cystic fibrosis, there are more than 1,800 genetic diseases that could potentially be treated with PTC124, including hemophilia.
“There are literally thousands of genetic diseases that could benefit from this approach,” said lead researcher Lee Sweeney, PhD, Department of Physiology at the the University of Pennsylvania. “What’s unique about this drug is it doesn’t just target one mutation that causes disease, but a whole class of mutations.”
PTC124, an oral drug, works by attaching itself to the cell’s ribosome, which converts genetic information into proteins, bypassing the nonsense mutation. This enables the gene to be “read” correctly and prompts normal protein production. The drug does not fix the original genetic defect but ignores it. Patients would need to continue taking the pill throughout their lifetime to remain free of symptoms.
In experiments on mice with the nonsense mutation that causes DMD, treatment with PTC124 elicited production of dystrophin, the muscle development protein affected by DMD, and subsequently regenerated the animals’ muscles.
In safety trials in humans, the drug has not caused major side effects. The results of phase II trials on cystic fibrosis and DMD will be published in the near future.
The study, “PTC124 Targets Genetic Disorders Caused by Nonsense Mutations,” was published in the online edition of the journal Nature on April 22, 2007.
Source: The Times Online (UK edition) and PTC Therapeutics news release both dated April 23, 2007