The predictive value of models of neuromuscular disorders to potentiate clinical translation

Abstract

Neuromuscular disorders (NMDs) are a heterogenous group of rare inherited diseases that compromise the function of peripheral nerves and/or muscles. With limited treatment options available, there is a growing need to design effective preclinical studies that can lead to greater success in clinical trials for novel therapeutics. Here, I discuss recent advances in modelling NMDs to improve preclinical studies as well as two articles from this issue that work in parallel to enable a deeper understanding of a particularly rare NMD, known as X-linked myotubular myopathy.

Impactful disease research: a DMM year in review

“…We have been thrilled to see our vision for the front section (invited review-type material) of DMM come to fruition ( Patton, 2021 ). Regular readers of DMM will have noticed that we have made a concerted effort to ensure that each DMM issue has an Editorial that is topical and interesting to our disease biology community, covering subjects ranging from mouse and Drosophila models of human disease ( Clapcote, 2022 ; Sansom, 2022 ; Verheyen, 2022 ) to infectious disease ( Tobin, 2022 ; Mostowy, 2022 ) and the predictive power of models of neuromuscular disease ( van Putten, 2022 ). Our newly launched Perspective pieces have flourished this year.…”

Supporting the translation of multiscale research in rare disease

“…Key progress has also been made in testing new therapeutic strategies for the ultra-rare sarcoma desmoplastic small round cell tumour, using patient-derived cell lines and patient-derived mouse xenograft models ( Smith et al, 2022 ; Zuco et al, 2023 ), and a new mouse model of rhabdomyosarcoma better recapitulates the human disease to enable the exploration of a wider range of therapies ( Nakahata et al, 2022 ). Rare muscular disorders are yet another area that has strongly benefitted from advanced model systems ( Crawford et al, 2022 ; Fernández-Costa et al, 2023 ; van Putten, 2022 ). Probing the pathomechanisms of these diverse diseases across scales – in a range of laboratory systems and along a spectrum of biological manifestations – is essential to further our understanding of these diseases that, individually, affect so few people, but together have an enormous impact on human health.…”