Evaluation for the Efficacy of Exon-Skipping Therapy Using In Vivo Assessment of Skeletal Muscle Function and Fragility.

Abstract

Splice-switching oligonucleotide (SSO) therapy is expected to be a promising treatment for muscular diseases such as Duchenne muscular dystrophy (DMD). Preclinical studies using animal models of muscle diseases are essential for the development of SSO therapy. In addition to the histological and biochemical analyses, an in vivo muscle torque measurement using supramaximal electrical stimulation has become a standard protocol for the evaluation of drug efficacy. Nevertheless, in order to accurately measure the torque production in animal models, there are some critical points that should be brought to attention. In this chapter, we describe detailed methods for in vivo muscle torque measurement in animal models for DMD, i.e., mdx52 mouse and canine X-linked muscular dystrophy in Japan (CXMD), that set the standard for reproducibility in this field.