As if to preempt the regulatory setbacks in Duchenne muscular dystrophy (DMD) that last week disappointed the field, a trio of preclinical studies emerged two weeks earlier showing that cutting out DMD mutations with gene editing might offer a viable alternative to the exon-skipping strategies that have dominated the pipeline. Now, the question is whether there's reason to believe the mouse studies will translate any better to the clinic.
The studies, published Dec. 31 in Science, provide in vivoproof of concept for the first time that CRISPR-Cas9 used postnatally can have a disease-modifying effect. Despite the hype around its therapeutic promise, the technology has so far proved itself primarily in research applications, for example, in modifying cells for in vitroscreening or creating animal models of disease.
Because CRISPR allows precise removal of segments or base pairs of DNA, it lends itself well to genetic diseases such as DMD, an X-linked genetic disorder caused by thousands of different mutations in the dystrophin gene.
The most common mutations occur in exon 51 and encode premature stop codons that halt normal transcription and result in truncated, non-functional dystrophin - a protein needed for contraction and relaxation of skeletal and cardiac muscle. The lack of dystrophin leads to a progressive decline in muscle function and premature death.
Eric Olson, professor of stem cell research and chair of research on cardiac birth defects at the University of Texas Southwestern Medical Center and principal investigator on one of the studies, told BioCentury that dystrophin needs its N- and C- terminal domains, but many of the regions