Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease
Copyright © 2019 Massachusetts Medical Society..
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.).
| Errataetall: |
CommentIn: N Engl J Med. 2019 Oct 24;381(17):1678-1680. - PMID 31597016 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:381 |
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| Enthalten in: |
The New England journal of medicine - 381(2019), 17 vom: 24. Okt., Seite 1644-1652 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Jinkuk [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.11.2019 Date Revised 24.10.2020 published: Print-Electronic CommentIn: N Engl J Med. 2019 Oct 24;381(17):1678-1680. - PMID 31597016 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa1813279 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM302040005 |
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| 500 | |a Date Revised 24.10.2020 | ||
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| 500 | |a CommentIn: N Engl J Med. 2019 Oct 24;381(17):1678-1680. - PMID 31597016 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Massachusetts Medical Society. | ||
| 520 | |a 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.) | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a MFSD8 protein, human |2 NLM | |
| 650 | 7 | |a Membrane Transport Proteins |2 NLM | |
| 650 | 7 | |a Oligonucleotides, Antisense |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Hu, Chunguang |e verfasserin |4 aut | |
| 700 | 1 | |a Moufawad El Achkar, Christelle |e verfasserin |4 aut | |
| 700 | 1 | |a Black, Lauren E |e verfasserin |4 aut | |
| 700 | 1 | |a Douville, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Larson, Austin |e verfasserin |4 aut | |
| 700 | 1 | |a Pendergast, Mary K |e verfasserin |4 aut | |
| 700 | 1 | |a Goldkind, Sara F |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Eunjung A |e verfasserin |4 aut | |
| 700 | 1 | |a Kuniholm, Ashley |e verfasserin |4 aut | |
| 700 | 1 | |a Soucy, Aubrie |e verfasserin |4 aut | |
| 700 | 1 | |a Vaze, Jai |e verfasserin |4 aut | |
| 700 | 1 | |a Belur, Nandkishore R |e verfasserin |4 aut | |
| 700 | 1 | |a Fredriksen, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Stojkovska, Iva |e verfasserin |4 aut | |
| 700 | 1 | |a Tsytsykova, Alla |e verfasserin |4 aut | |
| 700 | 1 | |a Armant, Myriam |e verfasserin |4 aut | |
| 700 | 1 | |a DiDonato, Renata L |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Jaejoon |e verfasserin |4 aut | |
| 700 | 1 | |a Cornelissen, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Pereira, Luis M |e verfasserin |4 aut | |
| 700 | 1 | |a Augustine, Erika F |e verfasserin |4 aut | |
| 700 | 1 | |a Genetti, Casie A |e verfasserin |4 aut | |
| 700 | 1 | |a Dies, Kira |e verfasserin |4 aut | |
| 700 | 1 | |a Barton, Brenda |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Lucinda |e verfasserin |4 aut | |
| 700 | 1 | |a Goodlett, Benjamin D |e verfasserin |4 aut | |
| 700 | 1 | |a Riley, Bobbie L |e verfasserin |4 aut | |
| 700 | 1 | |a Pasternak, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Berry, Emily R |e verfasserin |4 aut | |
| 700 | 1 | |a Pflock, Kelly A |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Reed, Chantal |e verfasserin |4 aut | |
| 700 | 1 | |a Tyndall, Kimberly |e verfasserin |4 aut | |
| 700 | 1 | |a Agrawal, Pankaj B |e verfasserin |4 aut | |
| 700 | 1 | |a Beggs, Alan H |e verfasserin |4 aut | |
| 700 | 1 | |a Grant, P Ellen |e verfasserin |4 aut | |
| 700 | 1 | |a Urion, David K |e verfasserin |4 aut | |
| 700 | 1 | |a Snyder, Richard O |e verfasserin |4 aut | |
| 700 | 1 | |a Waisbren, Susan E |e verfasserin |4 aut | |
| 700 | 1 | |a Poduri, Annapurna |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Patterson, Al |e verfasserin |4 aut | |
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| 700 | 1 | |a Berde, Charles B |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Timothy W |e verfasserin |4 aut | |
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