DYS-HAC-iPS cells: the combination of gene and cell therapy to treat duchenne muscular dystrophy.

摘要

Duchenne muscular dystrophy (DMD), one of the most prevalent pediatric genetic disorders (1 in 3,500 newborns), is caused by point mutations or deletions in the gene encoding dystrophln, a major component of the cytoskeleton of muscular fibers. Disruption of dystrophin results in structural instability within cardiac and skeletal muscle and accelerates turnover of the myogenic stem cell pool, ultimately leading to death in afflicted individuals. Gene transfer approaches to treat DMD are hampered by the very large size of the dystrophin locus (2.4 Mb) and the limited penetration into muscle by therapeutic viral vectors carrying the mini-dystrophin gene or exon-skipping constructs. Furthermore, obtaining autologous myogenic progenitors for use in DMD patients presents a particularly difficult challenge for the development of cell-based therapies.