Researchers in the United States have shown that genetically caused muscular dystrophy in dogs could be corrected using genetic editing tools. Muscular dystrophy is one of the most common fatal genetic conditions seen in children and is also seen in dogs.
This encouraging finding has raised hopes for thousands of children around the world who suffer from Duchenne muscular dystrophy. The study results appeared in the latest issue of the journal Science.
This new study is hailed as a landmark study that is the first to show beneficial effects of treating muscle dystrophy in large mammals.
Muscle dystrophy typically is a muscle wasting disorder that is genetically predicted and cripples the patient since birth and progresses until the child dies of respiratory, cardiovascular and other complications usually by the age of 30 years.
The problem usually lies within a gene on the X chromosome. Around one in 3,500 boys are affected by this condition. Males are affected because they have a single X chromosome.
This gene makes a protein called dystrophin that is important to make the muscle fibres strong. If the protein is missing or is not normally produced, the muscles of the body including the heart, diaphragm etc. tend to waste away and weaken with time.
If this method of genetically editing the mutations to remove the dystrophy works for other large animals, soon a clinical trial could be launched for patients with Duchenne muscular dystrophy, believe the scientists.
This new study from the team led by Eric Olson at the University of Texas Southwestern Medical Center uses Crispr-Cas9 – a gene editing tool to correct mutations in the dystrophin gene. Their study subjects were four one-month-old puppies.
The team engineered viruses to carry the edited genetic codes into the cells. These viruses target the mutated genes and remove it and the cell repair mechanism seals the corrected region. The team collaborated with the Royal Veterinary College, in London.
Leonela Amoasii, one of the team members said that she injected 20 trillion of these engineered viruses into the lower leg muscles of the beagle puppies. These puppies were known to carry the muscular dystrophy mutations. Six weeks later the levels of dystrophin were measured and up to 60 percent of the dystrophin was restored in some muscle fibres. Studies have shown that even a 15 percent of the normal levels of dystrophin could significantly help patients with muscle dystrophy.
Another two beagle puppies were infused with high or low dose of the Crispr gene editing molecules directly into their blood. Eight weeks later their muscles were again examined. This method showed a variable uptake of the edited molecules in different tissues and thus the levels of dystrophin also varied between 3 and 90 percent in skeletal muscles.
Dystrophin levels were 58 percent and 92 percent of normal levels respectively in the diaphragm and heart muscles. Olson said that the uptake of the edited gene in the heart and diaphragm muscles is encouraging.
As a next step the team plans more extensive studies among dogs to see if these benefits actually last. Long term studies in the animals would mean permissions to start these trials in humans too added Olson.
Kate Adcock, director of research and innovation at Muscular Dystrophy UK welcomed these results from the “proof of concept” study but said much more needs to be explored before it could be tried on humans.