Duchenne muscular dystrophy (DMD) is a genetic condition that affects both skeletal and cardiac muscle. The condition is a result of a mutation in the dystrophin gene, which leads to muscle cells not being able to produce a critical protein that helps hold muscle cells and tissue together. As a result of this, muscle tissue is continuously damaged and ultimately replaced with inflexible fibrous scar tissue, leading to patients becoming wheelchair-bound in their teenage years. As there is no current cure for this devastating disease, there is a large amount of research being conducted using gene editing in an attempt to find ways to fix the genetic mutation. A new research study from the Technical University of Munich has found a new gene-editing therapy for DMD in pigs that could have potential use in humans.
The researchers used the CRISPR-Cas9 system in order to perform genetic editing in pigs affected with DMD. The CRISPR-Cas9 system is able to find certain locations in the DNA using a specific guide sequence that allows for the editing of a gene of interest. The system can cut out the region that is mutated and then re-bind the DNA strands together. The researchers successfully applied this system by injecting it into pig muscle which resulted in the production of a functional dystrophin protein. Therefore, the use of CRISPR-Cas9 was able to restore the production of a functional product in muscle cells that were unable to do so beforehand.
Image Source: Ed Reschke
The researchers then investigated the structure and function of the dystrophin protein that was able to be synthesized in the pig muscle cells. The synthesized dystrophin was structurally similar to the protein found in healthy tissue. More importantly, it was able to improve the ability of the pigs to remain upright and enhance muscle stabilization. This research performed in a pig is the first successful experiment to not only correct the inability to produce dystrophin but also lead to functional improvements in both the muscle and heart in a large animal model. In regard to this research field, work with gene editing to fix DMD has been done in small animal models, like mice, or modeled in a petri dish outside the animal; therefore, these findings are significant as being able to apply these same tools in a large animal is a huge jump forward.
This research is extremely promising as it helps support the notion that gene editing could be used as a therapeutic treatment in humans. It is important to note that both muscle and cardiac cells are rather long-living cells; therefore, if these cells can be treated and fixed then there is a real possibility of providing a more long-term benefit and improvement to patients. Having the ability to increase muscle strength and restore structure could translate into increased quality of life and mobility for DMD patients, which would be a huge step forward in the management of this disease.
Featured Image Source: VadimGuzhva
