Products
Eteplirsen (Sarepta Therapeutics Inc) was approved in the United States in 2016 (Exondys 51).
Structure and properties
Eteplirsen (C364H569N177O122P30, Mr = 10305.7 g/mol) is a phosphorodiamidate morpholino oligomer (PMO) that binds selectively to exon 51 of pre-mRNA. It is an antisense oligomer with a high molecular weight. The sequence is complementary to the segment in the pre-mRNA. The figure shows the basic PMO structure. Eteplirsen is an RNA analog containing a morpholine ring instead of ribose and a phosphorodiamidate linker instead of phosphodiester.
Effects
The cause of Duchenne muscular dystrophy is mutations in the gene for dystrophin. These are often deletions, for example in exon 50. Dystrophin is essential for muscle function. Duchenne muscular dystrophy is a severe disease that is fatal in young adulthood. Eteplirsen restores dystrophin protein expression by skipping or removing exon 51 in the pre-mRNA during splicing (exon skipping). As a result, exon 51 is no longer present in the mRNA and is not translated. The body is now able to produce a truncated but partially functional protein. This does not cure the disease, but it does reduce its severity.
Indications
For the treatment of Duchenne-type muscular dystrophy.
Dosage
According to the SmPC. The drug is administered intravenously or subcutaneously.
