New findings raise questions on process to identify R&D drugs for rare diseases

A study by US National Institutes of Health researchers has revealed surprising new insights into the process used to initially identify an  experimental drug now being tested in people with cystic fibrosis and  muscular dystrophy. Researchers emphasized the clinical implications of  their findings are unclear, but said the results suggest more work may  be needed to make sure the screening process to select promising agents  was not flawed by its effects on a firefly enzyme used as a marker. The  study was published this month in the Proceedings of the National  Academy of Sciences.

Over the past several years, an experimental drug called PTC124 has  generated excitement among those seeking treatments for inherited  diseases caused by a type of genetic alteration that leads to  production of abnormally short proteins. Scientists refer to such  alterations as nonsense mutations. About 10% of cystic fibrosis cases  and about 15% of Duchenne muscular dystrophy cases are thought to arise  from nonsense mutations. In addition, nonsense mutations may affect a  substantial portion of the approximately 25 million Americans suffering  from other rare, genetic disorders.

The enzyme that makes fireflies glow, called luciferase, is widely used  in biomedical experiments and in high-throughput screening often  utilized to discover drugs. In a positive reaction, the tested material  literally lights up.