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Personalized antisense oligonucleotides ‘for free, for life’ — the n-Lorem Foundation

Nature Medicine volume 29, pages 1302–1303 (2023)Cite this article

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In 2017, results from a clinical trial of the antisense oligonucleotide (ASO) nusinersen demonstrated potent effects in motor milestone responses and event-free survival in infants with spinal muscular atrophy, prompting early termination of the trial1. ASOs represent a powerful drug platform, but because of their exquisitely specific binding to RNA nucleotides, most potential disease-altering ASOs would likely never be profitable for pharmaceutical companies. With nearly 7,000 single-gene disorders2 and many more pathogenic mutations known in humans, the potential space for personalized ASOs is enormous3. Patient advocates have started connecting with research groups offering personalized ASOs and other disease-altering therapies, and are finding promising preclinical and clinical evidence of benefit in ‘n-of-1’ trials4. The challenge will be to scale personalized ASOs as drugs, to impact disease outcomes where possible and to learn which diseases do and do not show benefit if the effect of the mutation is reversed.

The n-Lorem Foundation was established in 2020 with the mission to apply the efficiency, versatility and specificity of ASO technology to charitably provide experimental medicines to treat patients with ultra-rare diseases. n-Lorem is committed to providing these ASOs to the patients for whom they are designed ‘for free, for life’, focusing on severely debilitating or life-threatening conditions for which there are ≤30 patients who could benefit from a drug. This is both an ethical and practical approach considering the risk/benefit ratio, and is mandated by US Food and Drug Administration (FDA) guidelines5.

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Fig. 1: n-Lorem workflow from the tertiary care center to treatment.

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Authors and Affiliations

  1. n-Lorem Foundation, Carlsbad, CA, USA

    Joseph G. Gleeson, C. Frank Bennett, Jeffrey B. Carroll, Tracy Cole, Julie Douville, Sarah Glass, Cedrik Tekendo-Ngongang, Amy C. Williford & Stanley T. Crooke

  2. Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA

    Joseph G. Gleeson

  3. Rady Children’s Institute for Genomic Medicine, San Diego, CA, USA

    Joseph G. Gleeson

  4. Ionis Pharmaceutical, Carlsbad, CA, USA

    C. Frank Bennett

  5. Department of Neurology, University of Washington, Seattle, WA, USA

    Jeffrey B. Carroll

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  1. Joseph G. Gleeson
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Corresponding author

Correspondence to Joseph G. Gleeson.

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Competing interests

J.G.G. is a consultant for Neurocrine, Shire-Takeda and Ionis Pharmaceuticals. J.F.B. is a full-time employee of Ionis Pharmaceuticals. S.T.C. holds founder stock in Ionis Pharmaceuticals.

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Gleeson, J.G., Bennett, C.F., Carroll, J.B. et al. Personalized antisense oligonucleotides ‘for free, for life’ — the n-Lorem Foundation. Nat Med 29, 1302–1303 (2023). https://doi.org/10.1038/s41591-023-02335-2

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