Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease
- PMID: 31597037
- PMCID: PMC6961983
- DOI: 10.1056/NEJMoa1813279
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.).
Copyright © 2019 Massachusetts Medical Society.
Figures
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Comment in
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Drug Regulation in the Era of Individualized Therapies.N Engl J Med. 2019 Oct 24;381(17):1678-1680. doi: 10.1056/NEJMe1911295. Epub 2019 Oct 9. N Engl J Med. 2019. PMID: 31597016 No abstract available.
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Oligonucleotide designed for ultimate personalized treatment.Nat Rev Neurol. 2019 Dec;15(12):687. doi: 10.1038/s41582-019-0286-x. Nat Rev Neurol. 2019. PMID: 31673092 No abstract available.
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