A team of researchers from Canada, the United States, and Sweden found that editing a gene involved in the production of proteins that promote muscle strength can alleviate symptoms in a mouse model of muscular dystrophy. In their paper published in the journal of Nature, the team described their experiments with mice and the new knowledge they learned.
Muscular dystrophy is a hereditary disease in which muscle mass is weakened, leading to weakness and eventually disability. Previous studies have shown that the disease is caused by a mutation in a gene called Lama2. This genetic mutation can lead to proteins that are not required for normal muscle growth, which also destroys the nerve myelin and causes nerve damage. Until now, various efforts targeting this gene have not brought much improvement to patients. In this new study, researchers have adopted a new approach - CRISPR gene editing.
The gene associated with this technology is called Lama1, which is also involved in protein production during muscle production and development. But different from Lama2, it can promote the production of another protein called laminin-α1 through gene-mediated editing, and it can also promote the production of muscle tissue.
The researchers tried this new approach on a mouse model. They point out that in order to promote muscle tissue production, CRISPR is needed to develop a gene activation system that can handle large viral vectors involved in this process without generating DNA double-strand breaks in the helical structure. The researchers report that testing genetic editing techniques on mice showed positive results. The degree of fibrosis in mice is reduced and the volume of muscle fibers is increased, which in some cases reduces or prevents the development of muscular dystrophy. They also found that treating mice that were paralyzed by disease enabled them to stand up and move around. Meanwhile, the nerve conduction velocity is also accelerated, which is a sign of reversal of myelin destruction.
Researchers claim that more research and testing techniques are required before human experiments, such as the need to identify additional adverse effects that may be caused by increased laminin-α1 production.
Reference
- Dwi U. Kemaladewi et al. A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene, Nature (2019). DOI： 10.1038/s41586-019-1430-x.