Rational selection of the monoclonal α-synuclein antibody amlenetug (Lu AF82422) for the treatment of α-synucleinopathies.

ABSTRACT: Amlenetug (Lu AF82422) is a human monoclonal antibody targeting α-synuclein in clinical development for multiple system atrophy. We describe a series of studies that characterize its functional properties and supported its selection as a viable clinical candidate. Amlenetug inhibits seeding induced in mouse primary neurons by various α-synuclein fibrillar assemblies and by aggregates isolated from MSA brain homogenate. In vivo, both co-injection of amlenetug with α-synuclein assemblies in mouse brain and peripheral administration inhibit α-synuclein seeding. Amlenetug inhibits uptake of α-synuclein seeds as well as accumulation of C-terminal truncated α-synuclein seeds and demonstrates binding to monomeric, aggregated, and truncated forms of human α-synuclein. The epitope of amlenetug was

SUBMITTER: Kallunki P 

PROVIDER: S-EPMC12098740 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature