The gene editing technique, which can be used on any mutation type, has shown promise in mouse models.

Muscular dystrophy (MD) is a disease that involves progressive loss of muscle mass along with increasing weakness. It is caused by a range of gene mutations that lead to reduce production of the proteins required to form and retain healthy muscles. There are many forms of MD caused by a variety of mutations. Some affect children, while others don’t appear until adulthood.

Congenital muscular dystrophy type 1A (MDC1A) is one form of the disease caused by mutations in the Lama2 gene. It affects both boys and girls and is present at birth or before age 2. There are over 350 identified MDC1A-causing Lama2 mutations for this form of MD alone, requiring multiple therapies that need to be evaluated for each mutation.

Research at the Hospital for Sick Children (SickKids) in Toronto have gotten around this challenge by using CRISPR gene editing technology to modify the related gene Lama1. Increasing the expression of Lama1 was found to prevent paralysis in pre-symptomatic mice and reverse disease progression in animals that had already developed symptoms. The researchers believe this approach could be used for all patients suffering from MDC1A regardless of the mutation type driving their disease.

To develop the treatment, the researchers had to overcome a significant problem first: the viral vectors typically used to deliver gene therapies could not contain the very large Lama1 gene. Their solution was to use CRISPR to develop a gene-activation system that increases the expression of Lama1 without making double-stranded breaks in DNA.

In addition to showing promise as a treatment for MDC1A, the research believe this approach may also be effective for the treatment of other forms of MD, such as Duchenne muscular dystrophy (DMD), which is the most common form of the disease, perhaps in combination with a second gene therapy that corrects the specific mutation for DMD.