Perhaps understandably, you might think of viruses as nasty, disease-causing microbes that we want out of the body. But they’re not all bad, and some have their uses, as evidenced by this extremely encouraging new study which enlisted them to help treat dogs with Duchenne muscular dystrophy (DMD). Now that this novel treatment, a type of gene therapy, has proven to be safe and effective in animals, human trials could be on the horizon.
“This is the most common muscle disease in boys, and there is currently no effective therapy,” lead researcher Dongsheng Duan said in a statement. “This discovery took our research team more than 10 years, but we believe we are on the cusp of having a treatment for the disease.”
DMD, the most common type of muscular dystrophy, is caused by a mutant gene for the protein dystrophin. The resulting lack of this protein causes muscle cell degeneration, and the progressive loss of this tissue ultimately leads to debilitating movement and breathing problems.
With advances in science, there have been some encouraging developments in the field of gene therapy, which aims to edit or replace such faulty bits of disease-causing DNA. For example, there has been a trial in the U.K. investigating its potential to treat patients with cystic fibrosis, which showed some benefits. The problem with DMD, however, is that the gene for dystrophin is massive; so big that scientists struggled to work out how they would deliver a functional replacement to affected cells.
One of the major techniques scientists use in gene therapy is to engineer a harmless virus, or vector, to carry the therapeutic gene inside target cells, but dystrophin’s sheer size meant this wasn’t feasible. But the researchers, from the University of Missouri, found a way through this obstacle. They realized that using the entirety of the dystrophin gene in its native form wasn’t necessary, and worked out a way to miniaturize it without losing function.
“We removed functionally less important regions and re-assembled a synthetic gene that only includes regions essential to muscle,” Duan told IFLScience. “Our synthetic microgene is only around one-third of the size [of dystrophin].”
Earlier work showed that this microgene was capable of protecting muscles of diseased mice from wastage, but it took a considerable amount of time to develop a technique suitable for effective delivery in larger animals. They ended up using a vector called adeno-associated virus (AAV), a common choice due to its lack of pathogenicity and the precise manner in which it inserts genes into host cells, reducing the risk of disrupting bits of DNA that could lead to cancer.
As described in Human Molecular Genetics, after injecting three two-month-old affected dogs with the engineered virus, the gene was successfully delivered to all muscles throughout the body without negatively affecting muscle growth. Although the dogs were showing signs of disease when the therapy was given, several months on they are now developing normally, demonstrating the importance of getting in there early for the best chances of treatment success.
Importantly, the scientists didn’t note any serious side effects, and the therapy seemed to be well-tolerated by the animals. Duan told IFLScience that the researchers did, however, have to use immune system-suppressing drugs for a short period to reduce the risk of the body attacking the virus-infected cells, which has limited the use of AAV in gene therapy before.
But all in all, these indications of safety and efficacy will hopefully mean that human trials won’t be too far round the corner.