Journal
HUMAN MOLECULAR GENETICS
Volume 27, Issue R2, Pages R163-R172Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddy171
Keywords
-
Funding
- Institut national de la sante et de la recherche medicale (INSERM)
- Agence nationale de la recherche (ANR - Chair of Excellence HandiMedEx)
- Association Monegasque contre les myopathies (AMM)
- Duchenne Parent project France (DPPF)
Ask authors/readers for more resources
Duchenne muscular dystrophy (DMD) is a fatal genetic disorder characterized by progressive muscle wasting that has currently no cure. Exon-skipping strategy represents one of the most promising therapeutic approaches that aim to restore expression of a shorter but functional dystrophin protein. The antisense field has remarkably progress over the last years with recent accelerated approval of the first antisense oligonucleotide-based therapy for DMD, Exondys 51, though the therapeutic benefit remains to be proved in patients. Despite clinical advances, the poor effective delivery to target all muscle remains the main hurdle for antisense drug therapy. This review describes the antisense-based exon-skipping approach for DMD, from proof-of-concept to first marketed drug. We discuss the main obstacles to achieve a successful exon-skipping therapy and the latest advances of the international community to develop more powerful chemistries and more sophisticated delivery systems in order to increase potency, bioavailability and safety. Finally, we highlight the importance of collaborative efforts and early dialogue between drug developers and regulatory agencies in order to overcome difficulties, find appropriate outcome markers and collect useful data.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available