Evaluating the Therapeutic Potential of Geranylgeraniol (GGOH) in an iPSC-Derived Duchenne Muscular Dystrophy Disease Model
johnnie turner1, MEKALA GUNASEKARAN1, Sree Venigalla1, Hannah Littel1, Christina Pacak1, Peter Kang1
1Greg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School
Objective:
To determine whether geranylgeraniol (GGOH) treatment of isogenic induced pluripotent stem cell (iPSC)-derived Duchenne muscular dystrophy (DMD) and control myoblasts promotes rescue of myotube fusion and downstream cellular processes in the DMD cells.
Background:
GGOH is a metabolite in the mevalonate pathway that contributes to the synthesis of cholesterol and other non-sterol isoprenoids. Previous studies have shown that GGOH treatment in C2C12 cells promotes myogenic differentiation while suppressing skeletal muscleatrophy. GGOH also reduces statin-induced damage in cultured mouse myotubes and zebrafish muscle. As it currently stands, GGOH is taken as a dietary supplement by some individuals taking statins. Given its ability to mitigate statin-induced muscle damage, GGOH may have relevance in other muscle diseases. Prior work suggests that the mevalonate pathway may harbor therapeutic targets for DMD.
Design/Methods:
To explore the potential of GGOH as a therapeutic agent in DMD, isogenic iPSC-derived Duchenne muscular dystrophy (DMD) and control myoblasts were cultured and treated with a gradient GGOH doses during differentiation. Myotube fusion indices were quantified, and downstream molecular characteristics, including expression of myogenic and atrophy related genes, were assessed.
Results:
Preliminary findings suggest that GGOH may have some therapeutic effects.
Conclusions:
We anticipate that our ongoing studies will clarify the therapeutic potential of GGOH in DMD, setting the stage for further studies including human clinical trials.
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