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Theranostics 2020; 10(15):6854-6874. doi:10.7150/thno.44165 This issue Cite

Research Paper

Therapeutic potential of a TrkB agonistic antibody for Alzheimer's disease

Shudan Wang1,2,3, Hongyang Yao1*, Yihua Xu1,3*, Rui Hao4, Wen Zhang1, Hang Liu1,3, Ying Huang4, Wei Guo1,2,3✉, Bai Lu1,2,3✉

1. School of Pharmaceutical Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China, 100084.
2. Beijing Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China, 100070.
3. R&D Center for the Diagnosis and Treatment of Major Brain Diseases, Research Institute of Tsinghua University in Shenzhen, Shenzhen, Guangdong, China, 518057.
4. Center of Translational Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China, 200065.
*These authors have contributed equally to this work.

✉ Corresponding authors: Dr. Bai Lu. School of Pharmaceutical Sciences, Room B303, Tsinghua University, Beijing 100084, China, Tel: +86 62785101, E-mail: bai_luedu.cn; Dr. Wei Guo. School of Pharmaceutical Sciences, Room B302, Tsinghua Unive More

Citation:
Wang S, Yao H, Xu Y, Hao R, Zhang W, Liu H, Huang Y, Guo W, Lu B. Therapeutic potential of a TrkB agonistic antibody for Alzheimer's disease. Theranostics 2020; 10(15):6854-6874. doi:10.7150/thno.44165. https://www.thno.org/v10p6854.htm
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Abstract

Graphic abstract

Repeated failures of “Aβ-lowering” therapies call for new targets and therapeutic approaches for Alzheimer's disease (AD). We propose to treat AD by halting neuronal death and repairing synapses using a BDNF-based therapy. To overcome the poor druggability of BDNF, we have developed an agonistic antibody AS86 to mimic the function of BDNF, and evaluate its therapeutic potential for AD.

Method: Biochemical, electrophysiological and behavioral techniques were used to investigate the effects of AS86 in vitro and in vivo.

Results: AS86 specifically activated the BDNF receptor TrkB and its downstream signaling, without affecting its other receptor p75NTR. It promoted neurite outgrowth, enhanced spine growth and prevented Aβ-induced cell death in cultured neurons, and facilitated Long-Term Potentiation (LTP) in hippocampal slices. A single-dose tail-vein injection of AS86 activated TrkB signaling in the brain, with a half-life of 6 days in the blood and brain. Bi-weekly peripheral administration of AS86 rescued the deficits in object-recognition memory in the APP/PS1 mouse model. AS86 also reversed spatial memory deficits in the 11-month, but not 14-month old AD mouse model.

Conclusion: These results demonstrate the potential of AS86 in AD therapy, suggesting that neuronal and/or synaptic repair as an alternative therapeutic strategy for AD.

Keywords: Neurodegeneration, Therapy, Cognition, Antibody drug, Synaptic plasticity

Citation styles

APA
Wang, S., Yao, H., Xu, Y., Hao, R., Zhang, W., Liu, H., Huang, Y., Guo, W., Lu, B. (2020). Therapeutic potential of a TrkB agonistic antibody for Alzheimer's disease. Theranostics, 10(15), 6854-6874. https://doi.org/10.7150/thno.44165.

ACS
Wang, S.; Yao, H.; Xu, Y.; Hao, R.; Zhang, W.; Liu, H.; Huang, Y.; Guo, W.; Lu, B. Therapeutic potential of a TrkB agonistic antibody for Alzheimer's disease. Theranostics 2020, 10 (15), 6854-6874. DOI: 10.7150/thno.44165.

NLM
Wang S, Yao H, Xu Y, Hao R, Zhang W, Liu H, Huang Y, Guo W, Lu B. Therapeutic potential of a TrkB agonistic antibody for Alzheimer's disease. Theranostics 2020; 10(15):6854-6874. doi:10.7150/thno.44165. https://www.thno.org/v10p6854.htm

CSE
Wang S, Yao H, Xu Y, Hao R, Zhang W, Liu H, Huang Y, Guo W, Lu B. 2020. Therapeutic potential of a TrkB agonistic antibody for Alzheimer's disease. Theranostics. 10(15):6854-6874.

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