New antibody shows therapeutic effects in mice with Alzheimer's disease



According to a group of researchers from UTHealth Houston, a recently created agonistic antibody reduced the amyloid pathology in mice with Alzheimer's disease, indicating its promise as a potential treatment for the condition.

Researchers at McGovern Medical School at UTHealth Houston, under the direction of senior author Zhiqiang An, PhD, professor and holder of the Robert A. Welch Distinguished University Chair in Chemistry, discovered that a tetra-variable domain antibody directed against the triggering receptor expressed on myeloid 2 (TREM2), known as TREM2 TVD-lg, reduced amyloid burden, eased neuronal damage, and lessened cognitive decline in mice with Alzheimer's disease Today, Science Translational Medicine published the study.

An, head of the Texas Therapeutics Institute at The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, stated that "antibody-based therapy is a promising pharmacological approach for the treatment of Alzheimer's disease" (IMM). Creating methods to transfer antibody-based treatments across the blood-brain barrier for possible illness treatment is one of the main areas of focus at the Texas Therapeutics Institute.

Microglia—supportive cells that serve as scavengers in the central nervous system—express TREM2, a single-pass receptor. The clearance of amyloids that collect around amyloid-beta plaques, a characteristic of Alzheimer's disease, is greatly aided by microglia.

TREM2 has been implicated in the etiology of Alzheimer's disease in prior studies; however, more recent research suggests that increasing TREM2 activity may have therapeutic benefits, including enhanced cognition.

Ningyan Zhang, PhD, professor at the Texas Therapeutics Institute at IMM at McGovern Medical School and co-senior author, said: "By utilizing 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." This method of antibody engineering paves the way for the creation of AD treatments that successfully target TREM2.

Peng Zhao, PhD, a postdoctoral research fellow; Yuanzhong Xu, PhD, an assistant professor; Xuejun Fan, MD, PhD, a research scientist; Leike Li, PhD, a postdoctoral research fellow; Xin Li, a research associate; and Qingchun Tong, PhD, professor and Cullen Chair in Molecular Medicine, are additional authors from UTHealth Houston's IMM. The study's other contributor was Wei Cao, PhD, the Roy M. and Phyllis Gough Huffington Distinguished Professor of Anesthesiology at McGovern Medical School. The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences also employs An, Tong, and Cao as faculty members.

In addition to Hui Zheng, PhD, of Baylor College of Medicine in Houston, Hisashi Arase, MD, of Osaka University in Japan, LuLin Jiang, PhD, of Sanford Burnham Prebys Medical Discovery Institute in California, Yingjun Zhao, PhD, of Xiamen University in China, and Huaxi Xu, PhD, of Xiamen University and Chongqing Medical University in China are the other co-authors.

University of Texas Health Science Center at Houston

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