Oral medication restores missing protein in boys with muscular dystrophy

PTC124, an oral medication that changes the way muscle cells interpret genetic information, holds promise as a treatment for some patients with Duchenne muscular dystrophy (DMD), the Muscular Dystrophy Association has announced.

"We have lots of supportive care for children and adults with muscular dystrophy today," said Sharon Hesterlee, MDA's vice president of Translational Research, "but so far, this is the only therapy that's been effective at treating the root of the disease, the genetic defect itself. We're thrilled with these results."

PTC124 was developed by PTC Therapeutics of South Plainfield, N.J., with support from MDA. It tells cells to ignore a genetic mutation known as a premature stop codon, which is the cause of DMD in 13 percent of cases. Premature stop codons, also called nonsense mutations, interrupt protein synthesis before the full protein molecule has been constructed.

DMD, a devastating and fatal muscle disease, affects more than 10,000 Americans. It results from any of a number of mutations (flaws) in the gene for the muscle protein dystrophin, leading to the absence of this crucial molecule from muscle fibers. Because the gene is located on the X chromosome, the disease affects males almost exclusively.

Carsten Bonnemann, an MDA research grantee at the University of Pennsylvania and Children's Hospital of Philadelphia, announced today at the World Muscle Society International Congress in Italy that production of the needed dystrophin protein was restored in about half of 12 boys with DMD who took PTC124 for a month.

This group received a higher dose than did 26 boys in two earlier groups, who also showed biochemical indications of disease improvement. About half of them also began making dystrophin.

Results announced today show that the drug was well tolerated at all three dose levels and that target concentrations in the blood were achieved at the mid- and high-dose levels.

These studies suggest that the middle dose of PTC124 is as effective as the highest dose, at least over the course of a month's treatment.

"DMD is a disorder with a significant need for better treatment options and we are encouraged by the results we have seen to date with PTC124," said Brenda Wong, associate professor of Pediatrics and Neurology at Cincinnati (Ohio) Children's Hospital Medical Center and one of the trial's lead investigators. "Based on the findings from this study, we believe that the safety profile of PTC124 supports continued testing in longer-term studies."

MDA's Hesterlee said the "proof of principle" demonstrated in these DMD studies also implies a wide-ranging potential for PTC124 to treat over 1,800 genetic diseases, including other forms of muscular dystrophy, in cases where the cellular defect results from a premature stop codon.

MDA is a voluntary health organization that funds research and provides services in more than 40 neuromuscular diseases. Duchenne muscular dystrophy is a major focus for MDA.