Eteplirsen in the treatment of Duchenne muscular dystrophy

KRQ Lim, R Maruyama, T Yokota - Drug design, development and …, 2017 - Taylor & Francis
Drug design, development and therapy, 2017Taylor & Francis
Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in
3,500–5,000 male births that is characterized by progressive muscular deterioration. It is
inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the
DMD gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane
of muscle fibers. In September 2016, the US Food and Drug Administration granted
accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin …
Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500–5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the DMD gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame of DMD through specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients with DMD mutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed.
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