Phase 1 Study of Latozinemab in Progranulin-associated Frontotemporal Dementia

Overview

Journal Alzheimers Dement (N Y)

Date 2024 Feb 15

PMID 38356474

Authors

Michael Ward

Lawrence P Carter

Julie Y Huang

Daniel Maslyar

Balasubrahmanyam Budda

Robert Paul

Arnon Rosenthal

Affiliations

Soon will be listed here.

Abstract

Introduction: Heterozygous mutations in the 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 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 mutation (FTD-).

Results: Latozinemab demonstrated favorable safety and PK/PD profiles. Multiple-dose administration of latozinemab increased plasma and CSF PGRN levels in participants with FTD- 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-.

Highlights: 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- participants.

Citing Articles

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Fisher R, Torrente M Front Mol Neurosci. 2024; 17:1456052.

PMID: 39346681 PMC: 11427407. DOI: 10.3389/fnmol.2024.1456052.

Phase 1 study of latozinemab in progranulin-associated frontotemporal dementia.

Ward M, Carter L, Huang J, Maslyar D, Budda B, Paul R Alzheimers Dement (N Y). 2024; 10(1):e12452.

PMID: 38356474 PMC: 10865485. DOI: 10.1002/trc2.12452.

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