Research study with mices gene involving in producing proteins; that promote muscle strength in muscular dystrophy mice models could reduce symptoms. Muscular dystrophy is an inherited condition in which muscle mass attenuates, resulting in weakness and eventually disability.
Prior research has shown that caused by mutations in a gene called Lama2. The mutations prevent the gene from instigating the production of certain proteins that are necessary for muscle development. It also causes destruction of neuronal myelin coatings, leading to nerve damage.
Thus, efforts to target the gene with therapy methods have failed to provide much improvement for patients. Collectively, our data demonstrate the feasibility and therapeutic benefit of CRISPR–dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A.
Dystrophy in mice models
The researchers with this new effort tried this approach with mouse models. They note that to do so involved using CRISPR to develop a gene-activation system capable of dealing with the large viral vectors involved in the process one that would not make double-standard breaks in the helix. However, for many disorders it is important to investigate the therapeutic window and reversibility of symptoms.
The related gene is called Lama1 it, is involving in the production of proteins; that are part of muscle production and development. But unlike Lama2, it can be tweaked via gene editing to promote increased production of another protein called laminin-α1; also works to promote the generation of muscle tissue. The researchers reporting that testing the gene-editing technique on mice showing positive results. In muscular dystrophies, it has been hypothesized that fibrotic changes in skeletal muscle are irreversible.
Reductions in fibrosis
The mice saw reductions in fibrosis and larger muscle fiber size, which reducing or in some cases prevented symptoms from occurring. They also found that treating mice that had already become paralyzed due to symptoms allowed them to stand up and move around. However, postnatal upregulation of Lama1 is hampering by its large size; which exceeds the packaging capacity of vehicles that are clinically relevant for gene therapy.
The research study data demonstrating the feasibility and therapeutic benefit of CRISPR–dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. And the study finding that nerve conduction speed increasing; as well a sign that myelin coating destruction was being reversing. This approach has a broad applicability to a variety of disease modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.