PTC Therapeutics, South Plainfield, N.J., was granted orphan drug designation for PTC124 by the Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy due to a nonsense mutation in the dystrophin gene. PTC124 is a novel small-molecule drug currently being evaluated in phase I clinical trials involving healthy volunteers.

Nonsense mutations are single-point alterations in the genetic code that prematurely halt the translation process, producing a shortened, non-functional protein. About 10% of patients have the nonsense mutation in the dystrophin gene that prevents expression of the dystrophin protein. According to the company, PTC124 tricks the cellular machinery to bypass the nonsense mutation and continue the translation process, restoring the production of full-length, functional proteins.

“Our small molecule was selected to trick the cellular machinery to insert an amino acid at the stop codon and then continue on and make a full-length protein,” says Stuart Peltz, PhD, founder and CEO, PTC Therapeutics. “It’s almost like small molecule gene therapy and the idea is that the small molecule could theoretically work for many different diseases to the nonsense mutation,” says Peltz.

Early phase I studies showed that PTC124 is orally bioavailable and is generally well tolerated. Final results from the phase I trials are expected in early 2005. Pending FDA concurrence, the company expects to advance PTC124 into phase II studies in the first half of 2005. PTC124 is also being investigated for cystic fibrosis with a nonsense mutation of the CFTR protein and a phase II program is planned for the first half of 2005.

By Elizabeth Tolchin