New research marks the important addition to the preclinical model toolbox for the development and testing of novel therapies for DMD
— with sophisticated preclinical models generated by the MAGEC lab—a Phenomics Australia node specialising in in vivo genome engineering and disease modelling.
Every 7 September, World Duchenne Awareness Day unites people globally to raise awareness for Duchenne and Becker muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a devastating muscle-wasting disease with no cure. DMD is a genetic condition that causes the gradual loss of muscle function, impacting movement and daily activities. People with DMD do not correctly produce the dystrophin protein which is important for muscle strength, support and repair.
While many potential therapies have shown promise in early studies, very few have translated into clinical benefit. The current treatment options have been limited to corticosteroid therapy, which whilst delaying disease progression and improves lifespan of those with DMD, their prolonged use is associated with significant side effects.
To discover more effective therapies, we need to understand the breadth of DMD-causative mutations and small animal models are essential tools for development and preclinical testing. However so far, no one model perfectly replicates the DMD pathology, so using multiple models, with different disease severities and genetic background, in combination is a powerful approach for interrogating novel treatments.
Researchers from the University of Melbourne and Phenomics Australia’s Melbourne Advanced Gene Editing Centre (MAGEC) Node at the Olivia Newton-John Cancer Research Institute, have been working to address this gap with the generation of novel mouse models with varying mutation sites and a different genetic background.
“With support from Phenomics Australia and NCRIS, the MAGEC laboratory has developed advanced gene-editing technologies that are helping to transform medical research. A key focus has been Duchenne muscular dystrophy (DMD), a severe genetic disorder that leads to progressive muscle degeneration and greatly impacts quality of life. Using our gene-editing platforms, we are able to create accurate pre-clinical models of DMD efficiently and reliably. These models provide researchers with vital tools to study the underlying biology of the disease and to evaluate new therapeutic strategies.” Said Dr Andrew Kueh, Phenomics Australia Scientific Director, head of the MAGEC platform.
The team’s efforts, published in the Disease Models and Mechanisms Journal, have led the successful generation of a DMD mouse model with a CRISPR-induced deletion within exon 62 of the dystrophin gene (Dmd) and the first generated in BALB/c mice. The BALB/c.mdx62 mouse is a novel model of DMD with associated variations in the immune response and muscle phenotype, background strain and mutation location, compared with those of existing models.
It represents an important addition to the preclinical model toolbox for the development and testing of novel therapies for DMD. By broadening the spectrum of available tools, we improve our chances of identifying therapies that will truly translate into clinical success and change the lives of those living with DMD.
“By enabling faster and more precise development of these resources, we are equipping Australian researchers with the means to accelerate translational research and bring innovative treatments closer to patients. While our work directly supports the national research community, it also contributes to the global effort to improve health outcomes for individuals and families affected by DMD and other serious genetic conditions.” Dr Andrew Keuh
With an established track record and reputation for excellence, Phenomics Australia In Vivo Genome Engineering and Disease Modelling team uses techniques such as CRISPR-mediated mutagenesis, classical gene targeting, and transgenesis to create optimal tools for your research delivering a comprehensive service in genome modification. To meet the high demand for this platform, Phenomics Australia offers genome editing services through five nodes across Australia, operating at Monash, ANU, ONJCRI, SAHMRI and PeterMac.
