Myostatin Is a Quantifiable Biomarker for Monitoring Pharmaco-gene Therapy in Duchenne Muscular Dystrophy

Molecular Therapy. Methods & Clinical Development
Virginie MariotJulie Dumonceaux

Abstract

Recently, several promising treatments have emerged for neuromuscular disorders, highlighting the need for robust biomarkers for monitoring therapeutic efficacy and maintenance of the therapeutic effect. Several studies have proposed circulating and tissue biomarkers, but none of them has been validated to monitor acute and long-term drug response. We previously described how the myostatin (MSTN) level is naturally downregulated in several neuromuscular diseases, including Duchenne muscular dystrophy (DMD). Here, we show that the dystrophin-deficient Golden Retriever muscular dystrophy (GRMD) dog model also presents an intrinsic loss of Mstn production in muscle. The abnormally low levels of Mstn observed in the GRMD dog puppies at 2 months were partially rescued at both mRNA and protein level after adeno-associated virus (AAV)-microdystrophin treatment in a dose-dependent manner. These results show that circulating Mstn is a robust and reliable quantitative biomarker, capable of measuring a therapeutic response to pharmaco-gene therapy in real time in the neuromuscular system, as well as a quantitative means for non-invasive follow-up of a therapeutic effect. Moreover, a 2-year follow-up also suggests that Mstn could be a long...Continue Reading

References

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Citations

Sep 11, 2020·Journal of Clinical Medicine·Laura Le GallJulie Dumonceaux
Dec 20, 2020·International Journal of Molecular Sciences·Wei ChiuHao-Min Cheng
Aug 15, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Lin YinGuanhua Du

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Methods Mentioned

BETA
biopsy
biopsies
PCR
ELISA
PCRs

Clinical Trials Mentioned

NCT03368742
NCT03362502
NCT03375164
NCT00159250
NCT03789734

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