TUCSON, Ariz., Oct. 21, 2006 — An experimental compound developed by PTC Therapeutics of South Plainfield, N.J., with support from the Muscular Dystrophy Association (MDA), has shown promise as a treatment for Duchenne muscular dystrophy (DMD) in a clinical trial of boys with the disease, the Association announced today.
“We’re really encouraged by these exciting results,” said neurologist Valerie Cwik, MDA vice president – research and medical director. “We’re very gratified to see MDA’s support of PTC124 development translated into clinical activity in the fight against this terrible disease.”
MDA has awarded some $1.5 million to PTC Therapeutics for development of PTC124.
According to data presented today at an international DMD conference in London, in a study of 26 boys with DMD who took PTC124 by mouth for 28 days, significant biochemical improvements were observed, and parents and teachers reported functional improvements in some of the participants. The data were from clinical trial sites at Children’s Hospital of Philadelphia, Cincinnati Children’s HospitalMedicalCenter and the University of Utah in Salt Lake City.
DMD, the most common childhood form of muscular dystrophy, results from any of dozens of flaws (mutations) in the gene for dystrophin, a muscle protein that provides structural support and plays a role in chemical signaling in muscle fibers.
The gene is on the X chromosome, and the disease affects males almost exclusively. About one in 3,500 boys is born with the disorder.
Boys usually begin to have difficulty walking and climbing stairs in their toddler years and usually need a wheelchair full-time by their teens. Death typically occurs by age 30, from respiratory or cardiac muscle failure.
In about 15 percent of children with DMD, the dystrophin gene mutation generates stop signal that tells the muscle cell to stop making the dystrophin protein before it’s long enough to be functional. It’s this type of mutation that’s targeted by PTC124, which coaxes cells to ignore the stop signal and “read through” the rest of the genetic instructions, resulting in the synthesis of full-length dystrophin protein molecules.
Six trial participants, with an average age of 10, took PTC124 at a low dose; and 20, with an average age of 9, took it at a higher dose.
Increases in dystrophin expression were shown in muscle biopsies from a number of the boys participating in the trial. The level of creatine kinase, an enzyme that leaks out of damaged muscle cells into the bloodstream and is a rough indicator of muscle destruction, dropped significantly during PTC124 treatment.
The drug was well tolerated without significant side effects.
PTC Therapeutics plans to study PTC124 at a still higher dose beginning next month, if regulatory approvals can be obtained. The company plans a larger and longer (three- to six-month) study beginning during 2007.
“With such positive results so far, we’re very anxious for larger and more comprehensive trials to get underway,” Cwik said. “It will be particularly important to see if higher doses or a longer regimen will make PTC124 even more effective in boys with DMD.”
For more information about muscular dystrophy, see the MDA Web site at www.mda.org. MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases through programs of worldwide research, comprehensive services, and far-reaching professional and public health education
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