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: Sherifa A Hamed
• Journal: IDrugs : the investigational drugs journal (IDrugs) Vol. 9 Issue 11 Pg. 783-9 (Nov 2006) ISSN: 1369-7056 [Print] England
• PMID: 17096300 (Publication Type: Journal Article)

Chemical References

• Oxadiazoles
• Protein Synthesis Inhibitors
• ataluren

Topics

• Animals
• Clinical Trials as Topic
• Cystic Fibrosis (drug therapy)
• Humans
• Muscular Dystrophy, Duchenne (drug therapy)
• Oxadiazoles (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Protein Synthesis Inhibitors (adverse effects, pharmacokinetics, pharmacology, therapeutic use)