Without the defective exon, the muscle cells made a shortened dystrophin protein that was nonetheless functional, giving all of the mice more strength.
Duchenne muscular dystrophy is a progressive muscle-wasting disease that affects boys, putting them in wheelchairs by age 10, followed by an early death from heart failure or breathing difficulties. The disease is caused by defects in a gene that encodes a protein called dystrophin, which is essential for proper muscle function. Duchenne muscular dystrophy, affects approximately 1 in every 3,500 to 6,000 male births each year in the United States. Some types of MD are more prevalent in certain countries and regions of the world.
The teams were led by Charles A. Gersbach of Duke University, Eric N. Olson of the University of Texas Southwestern Medical Center and Amy J. Wagers of Harvard University.
“The papers are pretty significant,” said Louis M. Kunkel, a muscular dystrophy expert at Boston Children’s Hospital who discovered the dystrophin gene in 1986.
The dystrophin protein plays a structural role, anchoring each muscle fiber to the membrane that encloses the muscle-fiber bundle. The dystrophin gene, which guides the protein’s production in the cell, sprawls across about 1 percent of the X chromosome and is the largest in the human genome.
All three teams have filed for patents. But considerable work lies ahead before clinical trials can start. It is not clear how the human immune system would react to the components of the gene-editing system or to modified dystrophin proteins to which it has not been habituated.
If a gene therapy for muscular dystrophy can be developed, it will compete with the antisense oligonucleotide drugs that are already in clinical trials. These work on the same principle of avoiding damaged exons, but instead of cutting them out of the DNA, they force the exons to be skipped at a later stage of the protein manufacturing process.
The drugs do not target the heart muscles very well, however, and they must be given weekly. A gene therapy treatment should last longer.