A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies
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.
Authors
- Arsalan S. Haqqani (ORCID: https://orcid.org/0000-0003-2454-8989)
- Jinwon Jung (ORCID: https://orcid.org/0000-0002-7981-3316)
- Jung-Won Shin (ORCID: https://orcid.org/0000-0003-2155-9068)
- Laurent Pradier (ORCID: https://orcid.org/0000-0001-6022-0951)
- S. Pablo Sardi (ORCID: https://orcid.org/0000-0001-9805-3677)
- Christie E. Delaney (ORCID: https://orcid.org/0009-0005-6958-1725)
- Robert A. Rissman (ORCID: https://orcid.org/0000-0001-9245-8278)
- John J. McInnis (ORCID: https://orcid.org/0000-0002-4805-4214)
- Julia Maeve Bonner (ORCID: https://orcid.org/0000-0003-3551-9972)
- Daehae Song (ORCID: https://orcid.org/0000-0003-4367-3793)
- Byungje Sung
- Brian C. Mackness (ORCID: https://orcid.org/0000-0002-3587-5603)
- Miran Yoo
- Danica B Stanimirovic (ORCID: https://orcid.org/0000-0001-6678-407X)
- Alexandra T. Star (ORCID: https://orcid.org/0000-0001-9524-4312)
- Jin-Hyung Ahn
- Simon Dujardin (ORCID: https://orcid.org/0000-0002-5614-341X)
- Seung‐Hwan Kwon (ORCID: https://orcid.org/0000-0001-7965-5875)
- Sungwon An (ORCID: https://orcid.org/0000-0001-8828-1908)
- Dongin Kim (ORCID: https://orcid.org/0000-0003-2078-6138)
- Rajaraman Krishnan (ORCID: https://orcid.org/0000-0002-5189-4097)
- Jagdeep K. Sandhu (ORCID: https://orcid.org/0000-0002-0065-1335)
- Can Kayatekin (ORCID: https://orcid.org/0000-0002-4367-9645)
- Weon‐Kyoo You (ORCID: https://orcid.org/0000-0003-3833-798X)
- Yi Tang (ORCID: https://orcid.org/0000-0003-1597-0141)
- Sang Hoon Lee (ORCID: https://orcid.org/0000-0003-1202-917X)
- Donghwan Kim (ORCID: https://orcid.org/0000-0002-0139-2494)
- Jin‐Young Park (ORCID: https://orcid.org/0000-0003-4042-9779)
- Yihang Li (ORCID: https://orcid.org/0000-0002-4824-2274)
- Hyesu Yun
- Brian Spencer (ORCID: https://orcid.org/0000-0002-7486-1941)
- Hyeran Lee (ORCID: https://orcid.org/0000-0003-0722-419X)
- Ozge E. Tasdemir-Yilmaz
- Sumin Hyeon
Institutions
- University of Southern California (US)
- ABL Bio (South Korea) (KR)
- Sanofi (United States) (US)
- National Research Council Canada (CA)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-08-22
- DOI
- https://doi.org/10.1038/s41531-025-01117-6
- Citations
- 7
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 9.72