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Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease.

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.).

SUBMITTER: Kim J 

PROVIDER: S-EPMC6961983 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease.

Kim Jinkuk J   Hu Chunguang C   Moufawad El Achkar Christelle C   Black Lauren E LE   Douville Julie J   Larson Austin A   Pendergast Mary K MK   Goldkind Sara F SF   Lee Eunjung A EA   Kuniholm Ashley A   Soucy Aubrie A   Vaze Jai J   Belur Nandkishore R NR   Fredriksen Kristina K   Stojkovska Iva I   Tsytsykova Alla A   Armant Myriam M   DiDonato Renata L RL   Choi Jaejoon J   Cornelissen Laura L   Pereira Luis M LM   Augustine Erika F EF   Genetti Casie A CA   Dies Kira K   Barton Brenda B   Williams Lucinda L   Goodlett Benjamin D BD   Riley Bobbie L BL   Pasternak Amy A   Berry Emily R ER   Pflock Kelly A KA   Chu Stephen S   Reed Chantal C   Tyndall Kimberly K   Agrawal Pankaj B PB   Beggs Alan H AH   Grant P Ellen PE   Urion David K DK   Snyder Richard O RO   Waisbren Susan E SE   Poduri Annapurna A   Park Peter J PJ   Patterson Al A   Biffi Alessandra A   Mazzulli Joseph R JR   Bodamer Olaf O   Berde Charles B CB   Yu Timothy W TW  

The New England journal of medicine 20191009 17

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 f  ...[more]