A CRISPR-driven gene activation technique is shown to prevent and reverse disease symptoms in a mouse model of muscular dystrophy in a Nature paper that is published online this week.
Muscular dystrophies are a group of inherited muscle-wasting diseases. One subtype, congenital muscular dystrophy type 1A (MDC1A), is caused by mutations in the gene Lama2, which encodes laminin-α2. These mutations can make some peripheral nerves lose their protective myelin coating and disrupt the stability of muscle fibres. Rodent studies have shown that increasing expression of a related gene, Lama1 (which encodes laminin-α1), can help to ease symptoms in a mouse model of the disease, but the gene’s large size means that this effect is hard to achieve with standard gene therapy methods.
To address this issue, Ronald Cohn and colleagues used a CRISPR-mediated gene activation system to increase the expression of the laminin-α1 in a mouse model of MDC1A. When pre-symptomatic mice were treated, muscle wasting and paralysis symptoms were prevented, but, more importantly, the treatment also helped mice that had symptoms.
CRISPR is a versatile tool because it can be used to upregulate and downregulate the expression of key genes. The authors propose that in the future, combinatorial therapeutic approaches might help to treat this and other genetic disorders by ‘turning up’ protective genes and ‘turning down’ detrimental genes.