An increase in dystrophin was seen in a foot muscle in 61 percent of boys with nonsense-mutation DMD treated with ataluren in an MDA-supported study
An increase in levels of the dystrophin protein was seen after treatment with the experimental drug ataluren (originally called PTC124) in an MDA-supported, phase 2a, open-label trial of 38 boys with Duchenne muscular dystrophy (DMD) caused by a specific type of mutation in the dystrophin gene.
Ataluren, being developed by New Jersey-based PTC Therapeutics with MDA support, is designed to coax muscle cells to ignore (or "read through") an erroneous stop signal in the gene for the dystrophin protein, allowing a full-length, functional version of this protein to be produced.
Dystrophin is completely missing in the muscles of boys with DMD and partially missing in those with Becker muscular dystrophy (BMD). About 13 percent of children and young men with these disorders have mutations in the dystrophin gene known as premature stop codons or nonsense mutations. These mutations cause synthesis of the dystrophin protein to stop before a complete protein has been made.
PTC announced the results of the phase 2a trial, which was conducted at three U.S. from 2005 to 2007, in a Dec. 12, 2013, press release.
"The results of this phase 2a study support ataluren's activity as a dystrophin restoration therapy in nonsense- mutation Duchenne muscular dystrophy patients mediated by … read-through of nonsense mutations," said Stuart Peltz, CEO of PTC Therapeutics.
"These positive findings were the basis for the progression into a phase 2b study of ataluren in patients with nonsense-mutation DMD, which further demonstrated the potential of ataluren to slow the progression of nonsense-mutation DMD as measured by the six-minute walk test [which measures how far someone can walk in six minutes] and informed the design of our ongoing phase 3 study to confirm the safety and efficacy of ataluren."
The phase 2a trial results were published online Dec. 11, 2013, in the journal PLoS One. (The complete paper can be read without charge.)
About the phase 2a study
In the phase 2a study, 38 participants were given oral ataluren three times a day using one of three different dosage regimens.
All participants underwent a muscle biopsy of a small foot muscle (which was removed for analysis) to assess dystrophin levels prior to treatment. They then underwent a second biopsy, from the corresponding muscle in the other foot, on day 28 of treatment with ataluren.
Twenty-three of the 38 (61 percent) of the study participants showed increases in post-treatment compared with pre-treatment dystrophin levels.
Richard Finkel, a principal investigator on the phase 2a study, commented, "While there are challenges and limitations with currently available methods to assess change in dystrophin expression, this proof-of-concept study demonstrated that ataluren has the potential to increase dystrophin expression, and thereby modify the course of this severely disabling disease."
A 220-participant, phase 3 trial of ataluren is open at multiple sites in the U.S. and other countries for those who have nonsense mutations in the dystrophin gene and meet other study criteria.