Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: Current Status of Therapeutic Approaches.
Yuko Shimizu-MotohashiHirofumi KomakiNorio MotohashiShin'ichi TakedaToshifumi YokotaYoshitsugu AokiPublished in: Journal of personalized medicine (2019)
Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by progressive muscle weakness, is caused by the absence or a decreased amount of the muscle cytoskeletal protein dystrophin. Currently, several therapeutic approaches to cure DMD are being investigated, which can be categorized into two groups: therapies that aim to restore dystrophin expression, and those that aim to compensate for the lack of dystrophin. Therapies that restore dystrophin expression include read-through therapy, exon skipping, vector-mediated gene therapy, and cell therapy. Of these approaches, the most advanced are the read-through and exon skipping therapies. In 2014, ataluren, a drug that can promote ribosomal read-through of mRNA containing a premature stop codon, was conditionally approved in Europe. In 2016, eteplirsen, a morpholino-based chemical capable of skipping exon 51 in premature mRNA, received conditional approval in the USA. Clinical trials on vector-mediated gene therapy carrying micro- and mini- dystrophin are underway. More innovative therapeutic approaches include CRISPR/Cas9-based genome editing and stem cell-based cell therapies. Here we review the current status of therapeutic approaches for DMD, focusing on therapeutic approaches that can restore dystrophin.
Keyphrases
- duchenne muscular dystrophy
- crispr cas
- gene therapy
- genome editing
- cell therapy
- stem cells
- poor prognosis
- current status
- muscular dystrophy
- clinical trial
- binding protein
- skeletal muscle
- mesenchymal stem cells
- multiple sclerosis
- randomized controlled trial
- gene expression
- single cell
- high resolution
- long non coding rna
- study protocol
- protein protein
- small molecule
- bone marrow
- amino acid
- atomic force microscopy