Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease
| العنوان: | Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease |
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| المؤلفون: | Catherine J. Mummery, Anne Börjesson-Hanson, Daniel J. Blackburn, Everard G. B. Vijverberg, Peter Paul De Deyn, Simon Ducharme, Michael Jonsson, Anja Schneider, Juha O. Rinne, Albert C. Ludolph, Ralf Bodenschatz, Holly Kordasiewicz, Eric E. Swayze, Bethany Fitzsimmons, Laurence Mignon, Katrina M. Moore, Chris Yun, Tiffany Baumann, Dan Li, Daniel A. Norris, Rebecca Crean, Danielle L. Graham, Ellen Huang, Elena Ratti, C. Frank Bennett, Candice Junge, Roger M. Lane |
| المساهمون: | Neurology, Amsterdam Neuroscience - Neurodegeneration, Molecular Neuroscience and Ageing Research (MOLAR) |
| المصدر: | Nature medicine 29(6), 1437-1447 (2023). doi:10.1038/s41591-023-02326-3 Mummery, C J, Börjesson-Hanson, A, Blackburn, D J, Vijverberg, E G B, de Deyn, P P, Ducharme, S, Jonsson, M, Schneider, A, Rinne, J O, Ludolph, A C, Bodenschatz, R, Kordasiewicz, H, Swayze, E E, Fitzsimmons, B, Mignon, L, Moore, K M, Yun, C, Baumann, T, Li, D, Norris, D A, Crean, R, Graham, D L, Huang, E, Ratti, E, Bennett, C F, Junge, C & Lane, R M 2023, ' Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease : a phase 1b, randomized, placebo-controlled trial ', Nature Medicine, vol. 29, no. 6, pp. 1437-1447 . https://doi.org/10.1038/s41591-023-02326-3 Nature Medicine. Nature Publishing Group Nature Medicine, 29, 1437-1447. Nature Publishing Group |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Medicine, ddc:610, General Biochemistry, Genetics and Molecular Biology |
| الوصف: | Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPTRx) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPTRx. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPTRx or placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPTRx pharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPTRx and 12 to placebo. Adverse events were reported in 94% of MAPTRx-treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPTRx-treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPTRx groups. Clinicaltrials.gov registration number: NCT03186989. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1078-8956 0318-6989 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a4826e86379fe0686cd40f5d60108ba https://doi.org/10.1038/s41591-023-02326-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9a4826e86379fe0686cd40f5d60108ba |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 10788956 03186989 |
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