Titre : | Eteplirsen : LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |
Auteurs : | Collectif |
Type de document : | Article |
Editeur : | Bethesda - Maryland [USA] : National Institute of Diabetes and Digestive and Kidney Diseases, 02/2020 |
Langues: | Anglais |
Mots-clés : | article de type review ; dystrophie musculaire de Duchenne ; étéplirsen ; médicament ; oligonucléotide antisens |
Résumé : |
[Updated 2020 Feb 27]
Introduction Eteplirsen is synthetic antisense oligonucleotide designed to cause skipping of abnormal exons during synthesis of the dystrophin gene and that is used to treat Duchenne muscular dystrophy. Clinical experience with eteplirsen has been limited, but it has not been linked to serum enzyme elevations or to instances of acute liver injury with symptoms and jaundice. Background Eteplirsen (e” tep lir’ sen) is a synthetic antisense oligonucleotide designed to cause exon 51 skipping in the processing of mRNA for the dystrophin gene, which encodes an essential protein for muscle integrity. Patients with Duchenne muscular dystrophy typically have deletion mutations in exons [43 to 55] of the dystrophin gene, which disrupt the open-reading frame and the normal synthesis of the protein. Without dystrophin, muscle fibers become damaged during contraction resulting in inflammation and eventually replacement of muscle by fibrous and adipose tissue. Duchenne muscular dystrophy is an X-linked recessive disease that generally becomes clinically apparent by the age of 2 or 3 years, resulting in gradual loss of muscle and progressive disability often leading to loss of ambulation by age 10, ventilatory failure in early adulthood, and death in the 20s or 30s. In cell culture, antisense molecules were designed that allowed for skipping of the abnormal exon 51 found in 10% to 12% of patients with Duchenne muscular dystrophy and that replaced the defective dystrophin gene with a truncated but functional dystrophin molecule. In animal models, eteplirsen led to increases in truncated muscle dystrophin. In small clinical trials, eteplirsen was found to increase levels of dystrophin protein in muscle, on the basis of which it was approved for use in patients with Duchenne muscular dystrophy with a confirmed mutation in the dystrophin gene amenable to exon 51 skipping. Eteplirsen is available in solution in single dose vials of 100 mg or 500 mg (50 mg/mL). The recommended regimen is 30 mg per kg body weight once weekly by intravenous infusion. Side effects of eteplirsen include headache, fever, falls, abdominal pain, cough and nausea. Injection site reactions and hypersensitivity reactions including rash, pruritus, urticaria and skin exfoliation have occurred. Because eteplirsen is infused weekly, most patients have indwelling venous access catheters placed, which may pose a risk for complications of infection and septicemia. |
Lien associé : | Texte complet disponible sur le site Bookself NCBI |
Pubmed / DOI : | Pubmed : 32223120 |
N° Profil MNM : | 2020041 |
En ligne : | http://www.ncbi.nlm.nih.gov/pubmed/32223120 |