NOTES
Kim, JinkukHu, ChunguangMoufawad El Achkar, ChristelleBlack, Lauren EDouville, JulieLarson, AustinPendergast, Mary KGoldkind, Sara FLee, Eunjung AKuniholm, AshleySoucy, AubrieVaze, JaiBelur, Nandkishore RFredriksen, KristinaStojkovska, IvaTsytsykova, AllaArmant, MyriamDiDonato, Renata LChoi, JaejoonCornelissen, LauraPereira, Luis MAugustine, Erika FGenetti, Casie ADies, KiraBarton, BrendaWilliams, LucindaGoodlett, Benjamin DRiley, Bobbie LPasternak, AmyBerry, Emily RPflock, Kelly AChu, StephenReed, ChantalTyndall, KimberlyAgrawal, Pankaj BBeggs, Alan HGrant, P EllenUrion, David KSnyder, Richard OWaisbren, Susan EPoduri, AnnapurnaPark, Peter JPatterson, AlBiffi, AlessandraMazzulli, Joseph RBodamer, OlafBerde, Charles BYu, Timothy Weng2019/10/10 06:00N Engl J Med. 2019 Oct 9. doi: 10.1056/NEJMoa1813279.
Abstract
Genome sequencing is often pivotal in the diagnosis of rare diseases, but many of these conditions lack specific treatments. We describe how molecular diagnosis of a rare, fatal neurodegenerative condition led to the rational design, testing, and manufacture of milasen, a splice-modulating antisense oligonucleotide drug tailored to a particular patient. Proof-of-concept experiments in cell lines from the patient served as the basis for launching an "N-of-1" study of milasen within 1 year after first contact with the patient. There were no serious adverse events, and treatment was associated with objective reduction in seizures (determined by electroencephalography and parental reporting). This study offers a possible template for the rapid development of patient-customized treatments. (Funded by Mila's Miracle Foundation and others.).