Feng Yue, research associate scientist at Purdue University in West Lafayette, Ind., was awarded an MDA development grant totaling $175,409 over three years to evaluate the therapeutic potential of a protein called PTEN in Duchenne muscular dystrophy (DMD).
Please describe your current research in DMD.
DMD is a genetic disorder caused by an absence of dystrophin, a protein that helps keep muscle cells intact. In DMD, muscles are more susceptible to injury but they cannot keep up with repair, which eventually leads to muscle loss and weakness. We are working to develop potential therapies that promote regrowth of dystrophic muscle and, in turn, increase muscle strength.
The strategy we developed involves inhibiting the action of a natural protein called phosphatase and tensin homolog (PTEN), which limits muscle cell growth. In healthy muscle, the level of PTEN is very low, but it becomes very high in DMD muscles. Notably, lowering PTEN in healthy mouse muscle is sufficient to allow muscle to grow larger and stronger.
Using a preclinical mouse model of DMD, we will first study whether inhibiting PTEN by genetic deficiency of PTEN gene in muscle cells could boost muscle growth and increase muscle strength in DMD mice. We will then develop a safe, high-efficiency pharmacological approach to specifically deliver a well-known PTEN inhibitor to the skeletal muscle of DMD mice, and examine its effect on muscle functional recovery.
These studies may lead to the development of novel therapeutic strategies for clinical treatment of DMD.
Is this your first MDA grant?
Yes. This grant provides me with the necessary additional training and experience to develop and become a successful independent investigator performing cutting-edge translational biomedical research.
What inspired you to study DMD?
I met a family in the U.S. whose three boys all had DMD. Unfortunately, there are many individuals who have this life-threatening disease, and I really hope to be able to improve the lives of the individuals and families so they can live longer and better.
Why is it important that MDA continue to fund research in DMD?
So far, several therapeutic strategies have been developed and have shown promise in human clinical trials to treat DMD — especially the therapies based on exon skipping strategies. However, there are still significant challenges for widespread development of gene editing strategies due to the genomic features of DMD. Moreover, the long-term functional outcomes of these treatments remains poor. New strategies for ameliorating DMD symptoms are needed to boost the regrowth of damaged muscle and increase muscle strength in DMD patients, with the ultimate goal to improve their life quality and survival.
How will your research lead to treatments and cures?
Our study will first provide critical insights into the mechanistic basis by which direct inactivation of PTEN in muscle cells benefits the function of dystrophic muscle. More importantly, we will develop a potent pharmacological approach to target PTEN in dystrophic muscle, which could directly lead to the development of novel therapeutic applications for clinical treatment of DMD.
Does your work have any potential implications for other disease fields?
Yes. Our work of the establishment of peptide-specific nanoparticle delivery tool could indeed serve as a typical example for application of nanoparticle as drug delivery tool in the development of therapeutic strategies for other diseases.
To learn more about how MDA research is accelerating treatments and cures for DMD, visit mda.org.
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