Muscle Restoration Achieved in Mice with Duchenne Muscular Dystrophy

Utilizing a new kind of agent that targets a specific genetic defect, researchers have for the first time demonstrated restoration of muscle function in a mouse model of Duchenne's muscular dystrophy (DMD).

This development was achieved by a collaboration of researchers from at the University of Pennsylvania School of Medicine (Penn; Philadelphia, PA, USA), along with colleagues at PTC Therapeutics, Inc. (South Plainfield, NJ, USA), a biotech firm, and the University of Massachusetts Medical School (Worchester, MA, USA).

"This new class of treatment has the potential to help a large number of patients with different genetic diseases that have the same type of mutation, said senior author H. Lee Sweeney, Ph.D., chair of the department of physiology at Penn.

This genetic flaw causes from 5-15% (and in a few instances up to 70%) of individual cases of most inherited diseases, including DMD, cystic fibrosis, and hemophilia. The new drug, developed by PTC Therapeutics, and called PTC124, binds to the ribosome, a cellular component where the genetic code is translated into proteins, one amino acid at a time. The drug allows the ribosome to read through an error in the genetic code, called a premature stop codon, to correctly make whole proteins.

In DMD, patients are missing dystrophin, a protein that helps keep muscle cells intact. Approximately 15% of DMD patients do not make dystrophin because of the mutation. DMD ultimately affects all voluntary muscles, in addition to heart and breathing muscles.

PTC124 binds to ribosomes in all cell types within the MD mouse model, overriding the mutation in the dystrophin gene that signals it to stop production of the protein. Instead of halting, the full-length dystrophin protein is generated. The drug enables enough protein to be made to correct defects in the muscle of the DMD mouse, and at the same time, the drug does not prevent the ribosome from reading correct "stop” signals in the genetic code to make other necessary proteins.

"Enough dystrophin accumulated in the muscles of the MD mice so that we could no longer find defects in the muscles when we examined them,” stated Dr. Sweeney. "For all intents and purposes, the disease was corrected by treatment with PTC124.”

The drug allowed dystrophin to be produced in cells in which it was previously absent, to be delivered to the correct location at the cell membrane, and to induce restoration of muscle function in the muscles of the lab mice.

The study was published April 2007 online in the journal Nature.


Related Links:
University of Pennsylvania School of Medicine
PTC Therapeutics
University of Massachusetts Medical School