Eteplirsen
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| Trade names | Exondys 51 |
| Routes of administration |
Intravenous infusion |
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| Formula | C364H569N177O122P30 |
| Molar mass | 10305.738 |
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Eteplirsen (Exondys 51, Sarepta Therapeutics Inc.), also called AVI-4658, is a drug designed for treatment, but not a cure, of some mutations that cause Duchenne muscular dystrophy (DMD), a genetic degenerative muscle disease. Eteplirsen only targets mutations in a region implicated in 13% of DMD cases. After a controversial debate surrounding the efficacy of the drug, eteplirsen received accelerated approval from the US Food and Drug administration in late 2016. A year's worth of treatment with Eteplirsen is expected to cost approximately $300,000. A comprehensive review of the molecule and its clinical trials was published in early 2017.
Duchenne muscular dystrophy is caused when a mutation in the DMD gene changes the DMD RNA so that it no longer codes for functional dystrophin protein, usually due to a mutation that alters the reading frame of the RNA downstream of the mutation. If an exon with an appropriate number of bases lies near the mutation, by removing that exon the downstream reading frame can be corrected and production of partially functional dystrophin can be restored. This is the general strategy used for designing exon-skipping oligos for DMD; as there are 79 exons in the longest splice form of the dystrophin transcript, many different oligos are needed to address the range of mutations present in the population of people with DMD.
Eteplirsen is a morpholino antisense oligomer which triggers excision of exon 51 during pre-mRNA splicing of the dystrophin RNA transcript. Skipping exon 51 changes the downstream reading frame of dystrophin; giving eteplirsen to a healthy person would result in production of dystrophin mRNA which would not code for functional dystrophin protein but, for DMD patients with particular frameshifting mutations, giving eteplirsen can restore the reading frame of the dystrophin mRNA and result in production of functional (although modified by having an internal deletion consisting of both the patient's original defect, as well as the therapeutically skipped exon) dystrophin. Eteplirsen is given by intravenous infusion for systemic treatment of DMD.
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