Therapeutics: Dystrophin (DMD)

Mouse studies suggest exon skipping using tricyclo-DNAs (tcDNAs) could help treat DMD. tcDNAs are conformationally constrained antisense DNA analogs that spontaneously form nanoparticles. In a mouse model of DMD caused by a nonsense mutation in exon 23 of the dystrophin gene, exon 23-targeted tcDNA increased exon skipping and levels of dystrophin in skeletal muscle, cardiac and brain tissue compared with an exon-skipping 2'-O-methyl-modified oligoribonucleotide (2'-OMe) or phosphorodiamidate morpholino oligomer (PMO) targeted to exon 23. In the mouse model, IV administration of tcDNA increased muscle strength, respiratory function and cardiac systolic function and decreased behavioral abnormalities compared with control antisense molecules. Next steps include clinical testing of the tcDNA therapy. ...