PTC 124, solution of genetic diseases

Orphan Drug (PTC 124) for DMD and CF in the European Union
On July 7, the European Commission approved two indications for orphan drug PTC 124 (made by PTC Therapeutics, Inc.), allowing its use in the treatment of Duchenne muscular dystrophy (DMD) and cystic fibrosis (CF) caused by nonsense mutations.
According to a company news release, an estimated 10% of CF and 15% of DMD patients have these diseases as a consequence of nonsense mutations in the CF conductance regulator and dystrophin gene, respectively, that prematurely halt protein translation.
The single-molecule drug selectively modulates RNA use to allow bypass of the point mutation for the production of full-length, functional proteins. As such, it has the potential to address the underlying cause of disease, in contrast with current measures that may only temporarily slow disease progression or provide palliative benefit.
The approvals were based on the results of phase 1 studies in healthy volunteers showing that the drug is orally bioavailable and generally well tolerated, achieves target plasma concentrations that have been associated with activity in preclinical models, and does not induce ribosomal readthrough of normal stop codons.
Pharmacokinetic modeling of phase 1 data has led to the development of dosing regimens for use in phase 2 studies that are expected to begin in the U.S. later this year. The company is also working with patient advocacy groups and other organizations to develop studies in other regions of the world.
PTC 124 was previously granted fast-track status by the U.S. Food and Drug Administration for the CF indication and orphan drug indications in the treatment of CF and DMD on Dec. 9, 2004, and Jan. 27, 2005, respectively.
Potential indications currently under evaluation include hemophilia, neurofibromatosis, retinitis pigmentosa, epidermolysis bullosa, and lysosomal storage disorders.