Gene editing emerges as a new therapeutic strategy for Duchenne muscular dystrophy

Advances in gene editing technology have spurred considerable progress towards a treatment for Duchenne muscular dystrophy (DMD).  Although the disease is rare – affecting roughly 1 in 5,000 male births – its consequences are devastating: patients are confined to wheelchairs at an early age and often succumb to heart or respiratory failure in their twenties or thirties.  No treatments are currently available, but three separate labs have used CRISPR/Cas9, the much-publicized DNA editing system, to address the root cause of the disease.  DMD is caused by mutations that alter the function of a protein called dystrophin, which is required for proper muscle function.  It could be beneficial, therefore, to excise the regions of the gene that harbor those harmful mutations.  Encouragingly, mice with DMD that were treated in this manner saw a rise in functional dystrophin levels and alleviation of disease symptoms.

While the underlying science is sound, many hurdles still stand in the way of therapeutic relevance.  Previous gene editing efforts regarding DMD were performed in mouse embryos, but leading geneticists have recently called for a moratorium on such manipulation of human embryos until careful research identifies and mitigates any safety concerns.  One such strategy to circumvent this problem, as implemented by Dr. Amy Wagers, involves selective editing of the cells that continuously generate new muscle cells – muscle stem cells – in live mice.  Tailoring these changes to a specific group of cells should quell some of the (understandably worrisome) effects of having a DNA-altering virus coursing through your blood stream.  We have only begun to explore the implications of gene editing technology, but that’s why its therapeutic potential is so exciting.

Acknowledgments: Many thanks to Emma Vaimberg, a Research Associate at the Broad Institute of Harvard & MIT, for providing her expertise and commentary on the topic.

Managing Correspondent: Christopher Gerry

Original Research Articles: Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy – Science; In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy – Science; In vivo gene editing in dystrophic mouse muscle and muscle stem cells – Science

Media Coverage: Gene Editing Offers Hope for Treating Duchenne Muscular Dystrophy, Studies Find – New York Times

Related SITN Articles: CRISPR: A game-changing genetic engineering technique; DNA editing in humans: Biologists preach prudence

Correction (Jan. 13, 2016): An earlier version of this article mistakenly claimed that the three recent Science papers regarding DMD focused on embryonic gene editing in mice.  These papers, instead, discuss gene editing in live mice; experiments in mouse embryos had previously been performed in 2014.