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. 2023 Apr 24;29(6):1437–1447. doi: 10.1038/s41591-023-02326-3

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, Dosing and CSF sample collection for MAD part 1. CSF samples were obtained before the administration of study drug on days 1, 29, 57 and 85 for cohort A (10 mg MAPT_Rx or placebo monthly), cohort B (30 mg MAPT_Rx or placebo monthly) and cohort C (60 mg MAPT_Rx or placebo monthly) and on days 1 and 85 for cohort D (115 mg MAPT_Rx or placebo quarterly). The results of CSF samples obtained during screening and on day 1 (baseline) were averaged to serve as the baseline assessment, and the CSF samples on days 29, 57 and 85 served as 28 day, 56 day or 84 day post-dose trough samples. Two CSF samples were obtained in the post-treatment period, on either day 113 or day 141 for cohorts A and B and day 141 and day 197 for cohorts C and D. b, Patient flow during MAD part 1. Eligible patients were randomly assigned in a 3:1 ratio to receive the ASO MAPT_Rx or placebo in all cohorts.