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expert reaction to study using CRISPR in a mouse model of Duchenne muscular dystrophy

New research published in Nature Communications looks at ways of using the genome editing tool CRISPR to restore full-length dystrophin in mouse models of Duchenne muscular dystrophy.


Prof. Dominic Wells, Professor in Translational Medicine, Royal Veterinary College, University of London, said:

“Duchene muscular dystrophy (DMD) is a recessive X-linked fatal muscle wasting disease caused by mutations in the DMD gene that cause loss of the dystrophin protein.  This elegant study contributes to a growing body of evidence that CRISPR/Cas9 based gene editing has real promise in the treatment of Duchene muscular dystrophy and reports two different gene-editing strategies to restore dystrophin.  This was achieved by treating a specific strain of dystrophic mouse with a viral vector carrying the Cas9 gene under control of a muscle specific promoter.

“Muscle physiology demonstrated a functional improvement following intramuscular injection, which is important in considering the likely translation into patient benefit.  However, systemic delivery demonstrated only a patchy expression of dystrophin in the limb muscles and multiple muscles will need to be treated in Duchene muscular dystrophy.  Importantly, there was good expression in the heart.

“While this study demonstrates the promise of CRISPR/Cas9 gene editing for the treatment of Duchene muscular dystrophy, an increased efficiency will be required for human clinical trial.  Most importantly, as the authors note, it will be essential to investigate rigorously the effects of potential off-target events.”


Prof. Dame Kay Davies, Honorary Director of the MRC Functional Genomics Unit, University of Oxford, said:

“This is one of series of papers attempting to use CRISPR to correct the gene defect in Duchenne muscular dystrophy – this study has been done in mice, not humans.  The authors use whole-body delivery of the CRISPR vectors and show correction of the defect in mice for the first time which significantly improves function in muscle and targets the heart.  The approach depends on the use of adeno-associated viral vectors for delivery of CRISPR, and it will need to be assessed for off-target effects, but this study in mice is a very exciting step forward in the search for an effective treatment of Duchenne muscular dystrophy.”


Dr John Counsell, Research Associate in the Institute of Child Health Developmental Neurosciences Programme, UCL, said:

“Duchenne muscular dystrophy is caused by errors in the dystrophin gene, which leads to muscle weakness and fragility.  Gene therapy of muscular dystrophy has historically been challenging due to the extremely large size of dystrophin, so current treatments generally rely on smaller versions of dystrophin, which do not provide full functionality.

“This paper is important because it demonstrates that scarless ‘CRISPR’ gene editing can restore full-length dystrophin in a mouse model of Duchenne muscular dystrophy.  Despite success in repairing dystrophin, the treatment didn’t significantly improve muscle strength, so more work needs to be done to either improve the efficiency of repair, or to boost dystrophin production with additional therapeutic agents.  That said, the initial results are very encouraging and with further work this could potentially offer a new strategy for treating muscular dystrophy in patients.”


Prof. Darren Griffin, Professor of Genetics, University of Kent, said:

“We’re a long way from clinical application but there’s no doubt that the results of this study are exciting.  Duchenne muscular dystrophy is the worst kind of genetic disease where parents see their children waste away before their eyes and not reach adulthood.  The CRISPR/cas9 system has many applications but direct editing of disease genes is an obvious, and much needed one.

“In particular the results of this mouse study, including full- to near-full-length dystrophin protein expression levels are encouraging but, as the authors freely admit, they need to get the production levels higher and throughout the body.  The strength of this mouse study however is in its promise; it paves the way for further proof of principle trails in other animal models, many of which will involve assessing the safety of the procedure.  These, in turn, will pave the way for clinical application if all goes well.”


Dr Jenny Versnel, Director of Research, Muscular Dystrophy UK says:

“Muscular Dystrophy UK welcomes this important research from a well-respected group with considerable expertise in this field.  This study provides encouraging results that expand our understanding of CRISPR/Cas-9 strategies and their ability to effectively target the underlying mutation of a mouse model of Duchenne muscular dystrophy.  Although there are still unanswered questions regarding the longer term applicability of this technology, we look forward to future studies that will further enhance our knowledge and move us closer to the ultimate aim of evaluating its potential in people with Duchenne muscular dystrophy.”


Prof. Shirley Hodgson, Professor of Cancer Genetics, St George’s, University of London, said:

“This mouse study looks like a very exciting development in the search for a treatment for Duchenne muscular dystrophy, using the CRISPR technique which can correct many different mutations in the Duchenne gene.  This overcomes previous treatment methods which have been specific to only certain mutations in the gene.

“The treatment trialled here can be given systemically throughout the whole mouse body, and made to target muscle, so that unwanted mutations elsewhere which can sometimes result from this technique can be minimised.  This initial research in mice has shown that this treatment resulted in good expression of dystrophin (the functional protein that is lost in affected boys) in muscles, and show a corresponding increase in muscle strength.  Further research will be needed before this is ready for human trials to ensure that off-target mutations caused by this technique can be avoided, and that treatment in muscles is reliable with maintenance of the effect after treatment, avoiding the need for repeated treatments.”


* ‘Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy’ by Niclas E. Bengtsson et al. published in Nature Communications on Tuesday 14 February 2017. 


Declared interests

Prof. Dame Kay Davies: “Founder, Summit Therapeutics.”

Dr John Counsell: “I have no conflicting financial interests. I’m funded by Muscular Dystrophy UK to research CRISPR gene editing of Duchenne muscular dystrophy at UCL.

Prof. Darren Griffin: “No COI.”

Prof. Shirley Hodgson: “I have no conflict of interest.”

None others received.

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