| Literature DB >> 31597037 |
Jinkuk Kim1, Chunguang Hu1, Christelle Moufawad El Achkar1, Lauren E Black1, Julie Douville1, Austin Larson1, Mary K Pendergast1, Sara F Goldkind1, Eunjung A Lee1, Ashley Kuniholm1, Aubrie Soucy1, Jai Vaze1, Nandkishore R Belur1, Kristina Fredriksen1, Iva Stojkovska1, Alla Tsytsykova1, Myriam Armant1, Renata L DiDonato1, Jaejoon Choi1, Laura Cornelissen1, Luis M Pereira1, Erika F Augustine1, Casie A Genetti1, Kira Dies1, Brenda Barton1, Lucinda Williams1, Benjamin D Goodlett1, Bobbie L Riley1, Amy Pasternak1, Emily R Berry1, Kelly A Pflock1, Stephen Chu1, Chantal Reed1, Kimberly Tyndall1, Pankaj B Agrawal1, Alan H Beggs1, P Ellen Grant1, David K Urion1, Richard O Snyder1, Susan E Waisbren1, Annapurna Poduri1, Peter J Park1, Al Patterson1, Alessandra Biffi1, Joseph R Mazzulli1, Olaf Bodamer1, Charles B Berde1, Timothy W Yu1.
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.).Entities:
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Year: 2019 PMID： 31597037 DOI： 10.1056/NEJMoa1813279
Source DB: PubMed Journal: N Engl J Med ISSN： 0028-4793 Impact factor: 91.245