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. Much of the gene editing described above was performed in mouse embryos, but leading geneticists have recently called for a moratorium on such research in human embryos due to safety concerns. To circumvent this problem, Dr. Amy Wagers and her team have treated live mice by only editing the cells that continuously generate new muscle cells – muscle stem cells. Tailoring such changes to a specific group of cells should mitigate 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.
By Christopher Gerry, Harvard University
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.
Original Research Articles published in Science: Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy; In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy; In vivo gene editing in dystrophic mouse muscle and muscle stem cells
Original article published by: SITN, Harvard University
Featured image courtesy: http://www.genome-engineering.org/crispr/