McArdle Disease is one of the most common genetic skeletal muscle diseases, affecting up to 1 in 100,000 people (~1 in 158 people are carriers). McArdle Disease patients can have critical episodes of early fatigue when exercising, muscle pain (myalgia), myoglobinuria (when muscles break down and release myoglobin in urine, making it brown/red in colour), and then subsequent kidney failure.
Patients with McArdle Disease cannot utilise their glycogen energy stores in their skeletal muscles, due to a defect in the gene that produces the necessary enzyme. Despite a great deal of intensive investigation, no effective treatment for McArdle Disease has been found. Therefore there is a huge need for further research in this area.
We previously studied a naturally occurring sheep model of McArdle Disease, and were involved with investigating replacing the missing enzyme using a modified virus. This study yielded promising results. Since then, great improvements have been made using viruses to treat muscle diseases. Thus there is now even more impetus to pursue viral therapy for McArdle Disease.
However, a McArdle Disease mouse model to more readily and efficiently facilitate the evaluation of therapeutic approaches has been missing until now. Our collaborators in Spain (Drs Ramon Marti and Tony Andrew) recently created the first McArdle Disease mouse model which closely mimics the human disease. Our collaborative project will test delivering the missing enzyme to McArdle Disease mice using an adeno-associated virus (or delivering the fetal (brain) version of this enzyme), and we will target mice at different ages.
If successful, our research will be a significant step forward for the field, especially as this therapeutic approach should be effective for essentially all patients with McArdle Disease. We would eventually hope to test any positive treatment regime in the McArdle Disease sheep in Western Australia, which would be the next crucial step towards human clinical trials.