Re-Purposed Pharmacological Agents for Rapid Therapeutic Translation in Duchenne Muscular Dystrophy

Research Opportunity
PhD, Masters by Research
Department
Medicine and Radiology
Location
Western Health
Supervisor Email Number Webpage
Alan Hayes hayes.a@unimelb.edu.au Personal web page

Project Details

Duchenne Muscular Dystrophy (DMD) is a devastating degenerative neuromuscular disease that is currently incurable, poorly treated and in all cases fatal. While the pathophysiology of DMD is complex, we and others have established that mitochondrial dysfunction and oxidative stress are key features of the disease. More specifically, dysfunctional mitochondria generate toxic levels of reactive oxygen species, and as such, there is considerable potential for mitochondrial and anti-oxidative medicines to be useful therapies for DMD. This hypothesis is strongly supported by the pending release of the first indication-specific pharmacological mitochondrial therapeutic for the treatment of DMD in Europe and the USA, idebenone (Raxone®, Catena®), by Santhera Pharmaceuticals.

Translating a novel drug from “benchtop to bedside” is arduous and expensive – on average it takes 15 years and US$2.6 billion to translate a new medicine to patients. However, drug re-purposing (the investigation of already approved drugs to determine their safety and efficacy for treating a different condition) means they can be ready for clinical trials relatively quickly, expediting their review by regulatory bodies, and if approved, their integration into healthcare. In this project, we aim to determine whether two existing compounds have the potential to be re-purposed for DMD. We have evidence that the purine nucleotide adenylosuccinic acid, which has similar functional properties to idebenone, improves histopathological features of DMD muscle.

The aim of this project is to investigate known pharmacological modulators of mitochondrial function and oxidative stress that are already undergoing clinical testing in humans with the view to re-purposing them for DMD. The project will primarily use mouse models of DMD to pre-clinically evaluate skeletal muscle quality, function, histology, morphometry and mitochondrial metabolism. It will also involve culturing of human DMD muscle cells to explore mechanisms of action. Western blotting, immunohistochemistry, microscopy and enzyme activity assays will also be performed.


School Research Themes

Musculoskeletal



Research Opportunities

PhD, Masters by Research
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

Western Health

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