An et al. (2025). npj Parkinson s Disease. doi: 10.1038/s41531-025-01117-6
…PBS followed by a blocking process using 1% H 2 O 2 . Immunohistochemical detection was carried out with anti-pSer129-α-Syn antibody (S129) (Abcam, ab51250, 1:500) or anti-tyrosine hydroxylase antibody (Pel-Freez, 40101, 1:1000) using avidin-biotin complex (ABC) system (Vectastain ABC Elite Kit, Vector Laboratories, Burlingame, CA). The immunocomplexes were visualized with the chromogen 3,3′-diaminobenzidine…
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.