Phase 1 study of latozinemab in progranulin‐associated frontotemporal dementia
- Resource Type
- article
- Authors
- Michael Ward; Lawrence P. Carter; Julie Y. Huang; Daniel Maslyar; Balasubrahmanyam Budda; Robert Paul; Arnon Rosenthal
- Source
- Alzheimer’s & Dementia: Translational Research & Clinical Interventions, Vol 10, Iss 1, Pp n/a-n/a (2024)
- Subject
- disease‐modifying therapy
frontotemporal dementia
loss‐of‐function GRN mutation
latozinemab
phase 1 clinical trial
progranulin
Neurology. Diseases of the nervous system
RC346-429
Geriatrics
RC952-954.6
- Language
- English
- ISSN
- 2352-8737
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.