A new study has shown that editing a ‘modifier’ gene can prevent and reverse symptoms in a mouse model of congenital muscular dystrophy type 1A (MDC1A). More research is needed before this technique could be used in the clinic, but these findings are a positive step towards developing a potential treatment.
MDC1A is caused by mutations in the LAMA2 gene, which encodes a protein called laminin protein (also known as merosin). Laminin is important for stabilising muscle fibres and protecting some nerve cells. People with MDC1A don’t produce enough laminin, so their muscle and nerve cells become damaged over time.
Previous research has shown that increasing the activity of a related gene, LAMA1, reduces symptoms in mouse models of MDC1A. Because it can modify the severity of the condition, LAMA1 is known as a ‘modifier’ gene. Targeting a modifier gene could potentially benefit a wide range of patients as it isn’t specific to an individual’s mutation.
LAMA1 and LAMA2 are large genes, which makes them difficult to deliver using standard gene therapy methods. In this study, Dr Ronald Cohn and his team at The Hospital for Sick Children, Toronto, developed an alternative approach using genome editing technology.
The researchers designed their genome editing system to activate the LAMA1 gene in a mouse model of MDC1A. Some of the mice they treated were young enough not to have symptoms (pre-symptomatic), while the others had already developed limb paralysis and muscle scarring (fibrosis).
The genome editing treatment prevented muscle wasting and paralysis in the pre-symptomatic mice, and reversed paralysis and fibrosis in the older mice. This is an important finding as it shows that treatment is still beneficial at an advanced stage of disease.
One of the concerns with genome editing is the potential for unwanted edits being made by the ‘molecular scissors’. The researchers did not observe any unwanted edits in the mice, which is encouraging. However there’s still a lot to do before this could be tested in people with MDC1A. The next step will be to replicate the study in other animal models.
Dr Kate Adcock, Director of Research and Innovation at Muscular Dystrophy UK, said:
This is an exciting piece of research, which should give hope to people with congenital muscular dystrophy type 1A and their families. Targeting disease modifier genes in this way could benefit a wider range of patients, as the technique doesn’t depend on an individual mutation. This may not be a cure, but it’s a step in the right direction to finding a treatment for congenital muscular dystrophy type 1A.
The study was published in the scientific journal, Nature.