Skeletal muscles have been shown to display sporadic dystrophin-positive revertant fibers, both in animal models of DMD as well as in Duchenne patients. These dystrophin-positive fibers arise from spontaneous exon skipping events (alternative splicing of the mRNA) and lead to the production of an in-frame truncated dystrophin protein. The revertant events are thought to arise within a subset of muscle precursor cells which proliferate in response to the ongoing muscle degeneration and the expansion the clusters of revertant fibers is known to be dependent on active muscle regeneration.
The mechanisms by which revertant fibers arise and expand are not understood, and in the present study,

Toshifumi Yokoto et al. (Echigoya Y, Lee J, Rodrigues M, Nagata T, Tanihata J, et al. (2013) Mutation Types and Aging Differently Affect Revertant Fiber Expansion in Dystrophic Mdx and Mdx52 Mice. PLoS ONE 8(7): e69194. doi:10.1371/journal.pone.0069194) examined the effects of two types of mutation (mdx mice containing a nonsense mutation in exon 23 and mdx52 mice containing deletion mutation of exon 52) and aging on revertant fibers expansion and muscle regeneration. Their results demonstrate that revertant fiber expansion and muscle regeneration is influenced by both ageing and the specific type of mutation.

The translation of preclinical drug discover to clinical development has historically suffered a high attrition rate resulting in the majority of clinical studies failing in Phase I and Phase II clinical trials. The reasons for this are as varied and complex as the disease we aim to treat. To combat this, improvements are simultaneously needed in multiple areas; both preclinical and clinical as well as understanding the limitations of certain preclinical models as they relate to human disease. A recent paper by Kimmelman et al. (https://www.plosmedicine.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.1001489&representation=PDF) examines guidelines for in vivo experiments in animals in order to help improve the fidelity of preclinical studies. The researchers identified preclinical guidelines that met their predefined eligibility criteria, and offered 55 different recommendations for the design and execution of preclinical in vivo animal studies.