Tsoumpra, Maria K. National Centre of Neurology and Psychiatry
Fukumoto, Seiji University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Matsumoto, Toshio University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Takeda, Shin'ichi National Centre of Neurology and Psychiatry
Wood, Matthew J.A. University of Oxford
Aoki, Yoshitsugu National Centre of Neurology and Psychiatry
Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle degeneration, caused by the absence of dystrophin. Exon skipping by antisense oligonucleotides (ASOs) has recently gained recognition as therapeutic approach in DMD. Conjugation of a peptide to the phosphorodiamidate morpholino backbone (PMO) of ASOs generated the peptide-conjugated PMOs (PPMOs) that exhibit a dramatically improved pharmacokinetic profile. When tested in animal models, PPMOs demonstrate effective exon skipping in target muscles and prolonged duration of dystrophin restoration after a treatment regime. Herein we summarize the main pathophysiological features of DMD and the emergence of PPMOs as promising exon skipping agents aiming to rescue defective gene expression in DMD and other neuromuscular diseases. The listed PPMO laboratory findings correspond to latest trends in the field and highlight the obstacles that must be overcome prior to translating the animal-based research into clinical trials tailored to the needs of patients suffering from neuromuscular diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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ebiom_45_630.pdf 1.49 MB
Institute of Advanced Medical Sciences