Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease

By Jinkuk Kim, Chu Hu, C. Achkar, L. Black, J. Douville, A. Larson, Mary K. Pendergast, S. F. Goldkind, E. Lee, Ashley Kuniholm and 38 more. New England Journal of Medicine, 2019

624 citations recorded by the source corpus.

Summary 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.)

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/272c02c846deb3be72709f2acd0ba3987a6c0147

Citations in the corpus

• The next generation of evidence-based medicine (2023, neutral): “Conventional trials have been designed on the basis of the misconception that regulatory bodies may not accommodate more modern and diverse evidence from RWD, which is no longer the case 61,62 .”