| Autor: |
Michael Ward, Lawrence P. Carter, Julie Y. Huang, Daniel Maslyar, Balasubrahmanyam Budda, Robert Paul, Arnon Rosenthal |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Alzheimer’s & Dementia: Translational Research & Clinical Interventions, Vol 10, Iss 1, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2352-8737 |
| DOI: |
10.1002/trc2.12452 |
| Popis: |
Abstract INTRODUCTION Heterozygous mutations in the GRN gene lead to reduced progranulin (PGRN) levels in plasma and cerebrospinal fluid (CSF) and are causative of frontotemporal dementia (FTD) with > 90% penetrance. Latozinemab is a human monoclonal immunoglobulin G1 antibody that is being developed to increase PGRN levels in individuals with FTD caused by heterozygous loss‐of‐function GRN mutations. METHODS A first‐in‐human phase 1 study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple‐dose intravenous administration of latozinemab in eight symptomatic participants with FTD caused by a heterozygous loss‐of‐function GRN mutation (FTD‐GRN). RESULTS Latozinemab demonstrated favorable safety and PK/PD profiles. Multiple‐dose administration of latozinemab increased plasma and CSF PGRN levels in participants with FTD‐GRN to levels that approximated those seen in healthy volunteers. DISCUSSION Data from the first‐in‐human phase 1 study support further development of latozinemab for the treatment of FTD‐GRN. Highlights GRN mutations decrease progranulin (PGRN) and cause frontotemporal dementia (FTD). Latozinemab is being developed as a PGRN‐elevating therapy. Latozinemab demonstrated a favorable safety profile in a phase 1 clinical trial. Latozinemab increased PGRN levels in the CNS of symptomatic FTD‐GRN participants. |
| Databáze: |
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