Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease

Citation:

Kim J, Hu C, Moufawad El Achkar C, Black LE, Douville J, Larson A, Pendergast MK, Goldkind SF, Lee EA, Kuniholm A, Soucy A, Vaze J, Belur NR, Fredriksen K, Stojkovska I, Tsytsykova A, Armant M, DiDonato RL, Choi J, Cornelissen L, Pereira LM, Augustine EF, Genetti CA, Dies K, Barton B, Williams L, Goodlett BD, Riley BL, Pasternak A, Berry ER, Pflock KA, Chu S, Reed C, Tyndall K, Agrawal PB, Beggs AH, Grant PE, Urion DK, Snyder RO, Waisbren SE, Poduri A, Park PJ, Patterson A, Biffi A, Mazzulli JR, Bodamer O, Berde CB, Yu TW. Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease [Internet]. N Engl J Med 2019;

Date Published:

Oct 9

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.).

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.

Publisher's Version

Last updated on 10/10/2019