Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia.

ABSTRACT:

Background

Heterozygous loss-of-function mutations in the progranulin (PGRN) gene (GRN) cause a reduction in PGRN and lead to the development of frontotemporal dementia (FTD-GRN). PGRN is a secreted lysosomal chaperone, immune regulator, and neuronal survival factor that is shuttled to the lysosome through multiple receptors, including sortilin. Here, we report the characterization of latozinemab, a human monoclonal antibody that decreases the levels of sortilin, which is expressed on myeloid and neuronal cells and shuttles PGRN to the lysosome for degradation, and blocks its interaction with PGRN.

Methods

In vitro characterization studies were first performed to assess the mechanism of action of latozinemab. After the in vitro studies, a series of in vivo studies were perfo

SUBMITTER: Kurnellas M 

PROVIDER: S-EPMC10268535 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature