دورية أكاديمية
Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial
| العنوان: | Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial |
|---|---|
| المؤلفون: | Mummery, Catherine J, Borjesson-Hanson, Anne, Blackburn, Daniel J, Vijverberg, Everard GB, De Deyn, Peter Paul, Ducharme, Simon, Jonsson, Michael, Schneider, Anja, Rinne, Juha O, Ludolph, Albert C, Bodenschatz, Ralf, Kordasiewicz, Holly, Swayze, Eric E, Fitzsimmons, Bethany, Mignon, Laurence, Moore, Katrina M, Yun, Chris, Baumann, Tiffany, Li, Dan, Norris, Daniel A, Crean, Rebecca, Graham, Danielle L, Huang, Ellen, Ratti, Elena, Bennett, C Frank, Junge, Candice, Lane, Roger M |
| المصدر: | Nature Medicine , 29 pp. 1437-1447. (2023) |
| بيانات النشر: | NATURE PORTFOLIO |
| سنة النشر: | 2023 |
| المجموعة: | University College London: UCL Discovery |
| 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10181642/1/Tau-targeting%20antisense%20oligonucleotide%20MAPTsubRxsub%20in%20mild%20Alzheimers%20disease%20a%20phase%201b,%20randomized,%20placebo-controlled%20t.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10181642Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10181642/1/Tau-targeting%20antisense%20oligonucleotide%20MAPTsubRxsub%20in%20mild%20Alzheimers%20disease%20a%20phase%201b,%20randomized,%20placebo-controlled%20t.pdfTest https://discovery.ucl.ac.uk/id/eprint/10181642Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.93A29030 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |