Page 22 - eclipse - Autumn 2018

RESEARCH NEWS
黑料社 team in Duchenne muscular dystrophy breakthrough
黑料社 researchers, in collaboration with the University of Texas Southwestern (UTSW)
Medical Center, have made
a breakthrough in the search for a durable treatment for Duchenne muscular dystrophy (DMD).
The research succeeded in using gene editing techniques on dogs to restore the expression of the dystrophin protein absent in DMD patient鈥檚 muscles.
DMD results from mutations in the gene that encodes dystrophin, which helps protect muscle fibres and the heart when they contract. Affected children and dogs produce effectively no dystrophin protein, so their muscles and heart become damaged, leading to weakness, breathing problems and heart failure.
The 黑料社 team, led by Richard
Piercy (Professor of Comparative Neuromuscular Disease) along with 黑料社 neurologists, identified a naturally- occurring mutation in the dystrophin gene in a dog referred to 黑料社 Small Animal Referrals. Working with the dog鈥檚 relatives, SingleCut CRISPR gene editing was used to target a region of the subject鈥檚 DNA.
Harmless viruses encoding the gene editing protein CRISPR/Cas9 express the enzyme in muscle to cut the dog鈥檚 own DNA at a precise location in
the dystrophin gene through use of
a molecular guide. The body鈥檚 own processes then repair the cut, which results in removing negative effects of the mutation. The researchers demonstrated that dogs treated in this way had restored ability to produce large amounts of the dystrophin protein in their muscles and heart. In the dog with the highest dose, cardiac muscles had restored dystrophin protein to up to 92% of normal amounts after the single treatment.
The research was conducted according to the UK鈥檚 Animal Scientific Procedures Act with approval of the local Animal Welfare Ethical Review Board and in accordance with a specialist, independent Scientific Advisory and Ethics Board.
The team believes this is the first time that this form of gene editing therapy has been conducted after birth in an animal larger than a rodent. With further longer-term research, efficacy and safety testing, it is hoped that this breakthrough will have human application. This treatment may be a significant step toward developing a gene editing
therapy to repair genetic mutations for DMD, as well as a range of diseases caused by genetic mutations.
This preliminary research, published in Science (science.sciencemag.org/ content/362/6410/86), demonstrates an approach that could lead to an effective, one-time treatment for DMD for the most common genetic mutations affecting human patients.
Emphasising the significance of the breakthrough, Richard said: 鈥淚t is hugely exciting that through a single intravenous injection we鈥檝e been able successfully to modify the dogs鈥� own DNA so they start generating dystrophin protein again. There is more work to be done, but with this exciting breakthrough, we feel we are a significant step closer to finding an effective treatment.
鈥淎 great many genetic diseases affect humans, dogs and other species 鈥� many, like DMD 鈥� with tragic consequences and this form of gene editing treatment might well be applicable in many of them. We鈥檙e hopeful that we鈥檙e paving the way for future research into treating some of the most serious genetic conditions that affect us today.鈥�
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