2025-07-23 フランス国立科学研究センター(CNRS)
<関連情報>
- https://www.cnrs.fr/en/press/llama-antibodies-new-therapeutic-avenues-against-schizophrenia
- https://www.nature.com/articles/s41586-025-09265-8
ナノボディ療法は、NMDA受容体機能低下の行動障害を回復させます Nanobody therapy rescues behavioural deficits of NMDA receptor hypofunction
Mathieu Oosterlaken,Angelina Rogliardo,Tatiana Lipina,Pierre-André Lafon,Mireille Elodie Tsitokana,Mathilde Keck,Héloïse Cahuzac,Pierre Prieu-Sérandon,Séverine Diem,Cécile Derieux,Célia Camberlin,Chrystel Lafont,Damien Meyer,Patrick Chames,Franck Vandermoere,Philippe Marin,Laurent Prézeau,Denis Servent,Ali Salahpour,Amy J. Ramsey,Carine Bécamel,Jean-Philippe Pin,Julie Kniazeff & Philippe Rondard
Nature Published:23 July 2025
DOI:https://doi.org/10.1038/s41586-025-09265-8
Abstract
There is an urgent need for efficient and innovative therapies to treat brain disorders such as psychiatric and neurodegenerative diseases. Immunotherapies have proved to be efficient in many medical areas, but have not been considered to treat brain diseases due to the poor brain penetration of immunoglobulins1,2. Here we developed a bivalent biparatopic antibody, made of two camelid heavy-chain antibodies (called nanobodies)3, one binding to, and the other potentiating the activity of, homodimeric metabotropic glutamate receptor 2. We show that this bivalent nanobody, given peripherally, reaches the brain and corrects cognitive deficits in two preclinical mouse models with endophenotypes resulting from NMDA receptor hypofunction. Notably, these in vivo effects last for at least 7 days after a single intraperitoneal injection and are maintained after subchronic treatment. Our results establish a proof of concept that nanobodies can target brain receptors, and pave the way for nanobody-based therapeutic strategies for the treatment of brain disorders.
