The gene therapy significantly increased the muscle strength of dogs naturally affected by DMD, improving their ability to walk, run and jump.
'This is very encouraging, as current treatments for muscular dystrophy are merely palliative and patients are under constant medical care throughout their life,' said Dr John Counsell, who was not involved in the study but works at the Gene Transfer Technology Group at University College London.
DMD is a rare, progressive disease affecting all muscles of the body, including the heart and diaphragm. It is caused by mutations in the dystrophin gene, which leads to a deficiency of dystrophin protein. Dystrophin is important in supporting the muscle fibres during contraction; without it, the muscle fibres become damaged and eventually die.
As it is one of the largest human genes, it is technically challenging to insert the entire dystrophin gene into a viral vector, as is usually done for gene therapy. For this reason, the researchers in this study developed a gene therapy that delivers a smaller but functional version of the dystrophin gene (called micro-dystrophin). This was packaged into a non-pathogenic virus called an adeno-associated virus (AAV).
Twelve dogs with DMD received a single dose of the micro-dystrophin gene therapy and were monitored for up to two years. The researchers observed an increased amount of dystrophin protein in the dogs' muscles and a stabilisation of clinical symptoms in most of the dogs. There were no serious immune reactions to the gene therapy.
'The studies in dogs have been spectacular and exceeded our expectations,' said Professor George Dickson, who led the research at Royal Holloway University of London. My team has worked for many years to optimise a gene therapy medicine for DMD, and now the quite outstanding work of colleagues in France, in Genethon, in Nantes and in Paris has taken us close to clinical trials in DMD patients.'
In a separate study, a group of researchers from the US developed a micro-dystrophin gene therapy using a different type of AAV vector. They tested this in a recently established, severe DMD mouse model that is thought to be more like the human condition than the commonly used mdx mouse.
15 weeks after AAV injection, the researchers detected an increased amount of dystrophin protein in the mouse muscles. There were also improvements in muscle function and a reduction in muscle scarring and inflammation.
Whilst evaluating cardiac function, the researchers unexpectedly found pathological changes in the hearts of control mice, which meant that they were similar to the DMD hearts. For this reason, they could not evaluate the effect of the micro-dystrophin gene therapy on cardiac function and concluded that the mouse was not a good model for DMD-associated cardiomyopathy.