title: Drug evaluation: PTC-124--a potential treatment of cystic fibrosis and Duchenne muscular dystrophy.
abstract: PTC-124, a 1,2,4-oxadiazole compound, is in development by PTC Therapeutics Inc as an orally active small molecule that can override nonsense stop translation signals to produce full-length proteins. PTC-124 is currently being evaluated in phase II clinical trials against cystic fibrosis (CF) and Duchenne muscular dystrophy (DMD). The functional properties of PTC-124 are similar to the aminoglycoside antibiotic gentamicin, but the two compounds are chemically distinct and PTC-124 does not exhibit any antibiotic characteristics. In vitro experiments showed PTC-124 to be superior to gentamicin at ribosomal read-through of nonsense mutations. In vivo investigations revealed that PTC-124 was effective in restoring the production of full-length protein in animal models of CF and DMD. Phase I clinical trials reported that PTC-124 was well tolerated in healthy patients. The author concludes that the encouraging results observed to date make PTC-124 an attractive option for further well-designed, long-term human studies on larger sample populations. The author also predicts that if results continue to be positive, PTC-124 could also be trialed in other single gene disorders with nonsense mutations such as hemophilia, neurofibromatosis, retinitis pigmentosa, bullous skin diseases and lysosomal storage disorders.
authors.affiliation: Saudi German Hospital - Aseer, PO Box 2553, Khamis Mushayt 61961, Saudi Arabia. hamed_sherifa@yahoo.com
authors.forename: Sherifa A
authors.initials: SA
authors.lastname: Hamed
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy*; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*; D010069:Oxadiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011500:Protein Synthesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D010069:Oxadiazoles; D011500:Protein Synthesis Inhibitors; C515878:ataluren