In vitro models focusing on idiopathic inflammatory muscle disorders such as Pompe disease (PD) and infantile-onset Pompe disease (IOPD) are helping researchers uncover disease mechanisms and design new therapeutic strategies, according to a new review published in Cells.

The review also explores the recent progress that has been made in terms of simulating multicellular interactions of diseased muscle tissue and understanding the cell source, functionality, and throughput requirements for effective neuromuscular disease medication development.

“Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine,” the authors wrote. “A variety of in vitro models with varying complexity have been successfully introduced with a strong emphasis on the generation of neuromuscular interfaces.”

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Of particular interest to PD and IOPD researchers, studies using human induced pluripotent stem cells to derive skeletal myocytes are being conducted. These studies attempt to recreate the embryonic model of skeletal muscle cell development in vitro and explore the accumulation of lysosomal glycogen through lysosomal acid α-glucosidase defects. These studies also permit the genetic correction of mutations associated with diseases such as PD and IOPD.

The authors also describe the coculturing of myoblasts with immune cells in an effort to better understand autoimmune phenomena, elucidate the stages of disease progression, and ultimately identify possible targets for immunotherapy. To this end, in vivo conditions of various inflammatory muscular diseases are mimicked in vitro, with the aim of simulating the disease phenotypes as closely as possible. The ultimate goal is to develop regenerative therapies that will help patients with PD, IOPD, and other neuromuscular diseases regain muscle function.


Zschüntzsch J, Meyer S, Shahriyari M, et al. The evolution of complex muscle cell in vitro models to study pathomechanisms and drug development of neuromuscular disease. Cells. 2022;11(7):1233. doi:10.3390/cells11071233