纳米体治疗挽救NMDA受体功能低下的行为缺陷，这一成果由蒙彼利埃大学Philippe Rondard小组经过不懈努力而取得。相关论文于2025年7月23日发表在《自然》杂志上。

在这里，小组开发了一种二价双异位抗体，由两个骆驼重链抗体（称为纳米体）组成，一个与同二聚体代谢性谷氨酸受体2结合，另一个增强其活性。课题组人员发现，在两种由NMDA受体功能低下引起的内表型临床前模型中，这种外周给予的二价纳米体可以到达大脑并纠正认知缺陷。值得注意的是，单次腹腔注射后这些体内效应至少可持续7天，并在亚慢性治疗后维持。他们的研究结果证实了纳米体可以靶向大脑受体的概念，并为基于纳米体的治疗脑部疾病的治疗策略铺平了道路。

据了解，迫切需要有效和创新的治疗方法来治疗脑部疾病，如精神和神经退行性疾病。免疫疗法在许多医学领域已被证明是有效的，但由于免疫球蛋白的脑渗透能力差，尚未被认为可以治疗脑部疾病。

附：英文原文

Title: Nanobody therapy rescues behavioural deficits of NMDA receptor hypofunction

Author: Oosterlaken, Mathieu, Rogliardo, Angelina, Lipina, Tatiana, Lafon, Pierre-Andr, Tsitokana, Mireille Elodie, Keck, Mathilde, Cahuzac, Hlose, Prieu-Srandon, Pierre, Diem, Sverine, Derieux, Ccile, Camberlin, Clia, Lafont, Chrystel, Meyer, Damien, Chames, Patrick, Vandermoere, Franck, Marin, Philippe, Przeau, Laurent, Servent, Denis, Salahpour, Ali, Ramsey, Amy J., Bcamel, Carine, Pin, Jean-Philippe, Kniazeff, Julie, Rondard, Philippe

Issue&Volume: 2025-07-23

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 7days 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.

DOI: 10.1038/s41586-025-09265-8

Source: https://www.nature.com/articles/s41586-025-09265-8