{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["An S"],"funding":["NIA NIH HHS"],"pagination":["254"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12373799"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Parkinson's disease and multiple system atrophy are members of a class of devastating neurodegenerative diseases called synucleinopathies, which are characterized by the presence of alpha-synuclein (α-Syn) rich aggregates in the brains of patients. Passive immunotherapy targeting these aggregates is an attractive disease-modifying strategy, which must not only demonstrate target selectivity towards α-Syn aggregates, but also achieve appropriate brain exposure to have the desired therapeutic effect. Here we present preclinical data for SAR446159, a next-generation antibody for the treatment of synucleinopathies. SAR446159 is a bispecific antibody composed of an α-Syn-binding immunoglobulin and an engineered insulin-like growth factor receptor 1 binding single-chain variable fragment, acting as a shuttle to transport an antibody across the blood-brain barrier. SAR446159 binds tightly and preferentially to α-Syn aggregates and prevents their seeding capacity in vitro and in vivo. The binding properties of SAR446159 combined with its brain-shuttle technology make it a potent immunotherapeutic for treating synucleinopathies."],"journal":["NPJ Parkinson's disease"],"pubmed_title":["A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies."],"pmcid":["PMC12373799"],"funding_grant_id":["P30 AG066530"],"pubmed_authors":["Kim D","Star AT","Shin JW","Yun H","Lee H","Mackness BC","Dujardin S","Stanimirovic DB","Delaney CE","Sandhu JK","Hyeon S","Rissman RA","Sung B","Pradier L","Tang Y","An S","McInnis JJ","Sardi SP","Bonner JM","Park J","Jung J","You WK","Kayatekin C","Lee SH","Song D","Spencer B","Krishnan R","Haqqani AS","Li Y","Tasdemir-Yilmaz O","Ahn J","Kwon SH","Kim DB","Yoo M"],"additional_accession":[]},"is_claimable":false,"name":"A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies.","description":"Parkinson's disease and multiple system atrophy are members of a class of devastating neurodegenerative diseases called synucleinopathies, which are characterized by the presence of alpha-synuclein (α-Syn) rich aggregates in the brains of patients. Passive immunotherapy targeting these aggregates is an attractive disease-modifying strategy, which must not only demonstrate target selectivity towards α-Syn aggregates, but also achieve appropriate brain exposure to have the desired therapeutic effect. Here we present preclinical data for SAR446159, a next-generation antibody for the treatment of synucleinopathies. SAR446159 is a bispecific antibody composed of an α-Syn-binding immunoglobulin and an engineered insulin-like growth factor receptor 1 binding single-chain variable fragment, acting as a shuttle to transport an antibody across the blood-brain barrier. SAR446159 binds tightly and preferentially to α-Syn aggregates and prevents their seeding capacity in vitro and in vivo. The binding properties of SAR446159 combined with its brain-shuttle technology make it a potent immunotherapeutic for treating synucleinopathies.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-30T03:23:45.077Z","creation":"2026-06-30T03:16:24.658Z"},"accession":"S-EPMC12373799","cross_references":{"pubmed":["40847026"],"doi":["10.1038/s41531-025-01117-6"]}}