Patient-customized oligonucleotide therapy for a rare genetic disease
Kim J, Hu Chen, Moufawad El Achkar C, Black LE, Julie Douville, Allison R. Larson, Pendergast MK, Goldkind SF, Lee Ea, Ashley Kuniholm, Aubrie Soucy, Jai Vaze, Belur NR, Kristina Fredriksen, Iva Stojkovska, Alla V. Tsytsykova, Myriam Armant, DiDonato RL, Jaewoo Choi, Loes L. Cornelissen, Pereira Lm, Augustine EF, Genetti CA, Kira A. Dies, Bruce Barton, Loretta A. Williams, Goodlett BD, Riley Bl, Amy L. Pasternak, Berry Er, Pflock KA, Shu‐Hsun Chu, Charles B. Reed, Kimberly Tyndall, Agrawal Pb, Beggs Ah, P. Ellen Grant, Urion DK, Snyder RO, Waisbren SE, Annapurna Poduri, Park PJ, Adam P. Patterson, Alessandra Biffi, Mazzulli JR, Olaf A. Bodamer, Berde Cb, Yu Tw
Abstract
This remarkable case report - by authors from Boston Childrens Hospital and funded by Milas Miracle Foundation - describes the development and use of a patient-customised antisense oligonucleotide drug that was tailored specifically against the unique DNA sequence mutation in a 6-year old girl with Batten disease, a degenerative neurological disease due to neuronal accumulation of lipofuscin and characterised by intractable seizures. They first tested the drug ex vivo, using cell lines from the patient, then showed that systemic administration reduced the frequency of seizures and halted her previously deteriorating neurological function.