Scientists have developed a new promising potential treatment for Alzheimer’s disease.
According to a team of researchers from the University of Texas Health Houston, a newly created agonistic antibody decreased amyloid pathology in mice with Alzheimer’s disease, indicating its promise as a possible treatment for the condition.
TREM2 TVD-lg, a tetra-variable domain antibody targeting the triggering receptor expressed on myeloid 2 (TREM2), decreased amyloid burden, eased neuron damage, and alleviated cognitive decline in mice with Alzheimer’s disease, according to research headed by senior author Zhiqiang An, Ph.D., professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School at UTHealth Houston. The study was recently published in the journal Science Translational Medicine.
“Antibody-based therapy is a viable drug modality for the treatment of Alzheimer’s disease,” said An, director of the Texas Therapeutics Institute with The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM). “One of the major areas of focus at the Texas Therapeutics Institute is developing technologies to deliver antibody-based therapies across the blood-brain barrier for the potential treatment of the disease.”
TREM2 is a single-pass receptor expressed by microglia, which are supporting cells in the central nervous system that serve as scavengers. Microglia are important in the removal of amyloids that form clusters surrounding amyloid-beta plaques, which are a hallmark of Alzheimer’s disease.
While prior research has indicated that TREM2 is crucial in the pathophysiology of Alzheimer’s disease, the new study suggests that raising TREM2 activation may have therapeutic benefits such as improved cognition.
“By leveraging the unique antibody drug discovery capabilities at UTHealth Houston and collaborating with scientists with complementary expertise, we demonstrated the feasibility of engineering multivalent TREM2 agonistic antibodies coupled with TfR-mediated brain delivery to enhance microglia functions and reduce amyloid pathology in vitro and in vivo,” said co-senior author Ningyan Zhang, Ph.D., professor at the Texas Therapeutics Institute at IMM at McGovern Medical School. “This antibody engineering approach enables the development of effective TREM2-targeting therapies for AD.”
Reference: “A tetravalent TREM2 agonistic antibody reduced amyloid pathology in a mouse model of Alzheimer’s disease” by Peng Zhao, Yuanzhong Xu, LuLin Jiang, Xuejun Fan, Leike Li, Xin Li, Hisashi Arase, Yingjun Zhao, Wei Cao, Hui Zheng, Huaxi Xu, Qingchun Tong, Ningyan Zhang and Zhiqiang An, 7 September 2022, Science Translational Medicine.
The study was funded by the Cancer Prevention and Research Institute of Texas and the Welch Foundation.