GLP1R Agonist(AVVA)(GLP1R Agonist(AVVA)) - 药物靶点：GLP-1R_在研适应症：阿尔茨海默症，帕金森病_专利_临床

概要

基本信息

药物类型

化学药

别名-

靶点

GLP-1R

作用方式

激动剂

作用机制

GLP-1R激动剂(胰高血糖素样肽-1激动剂)

治疗领域

神经系统疾病内分泌与代谢疾病

在研适应症

阿尔茨海默症帕金森病

非在研适应症-

原研机构

Avva Pharmaceuticals Ltd.

在研机构

Avva Pharmaceuticals Ltd.

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 GLP1R Agonist(AVVA) 相关的临床结果

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100 项与 GLP1R Agonist(AVVA) 相关的转化医学

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100 项与 GLP1R Agonist(AVVA) 相关的专利（医药）

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14

项与 GLP1R Agonist(AVVA) 相关的文献（医药）

2024-12-01·DIABETES RESEARCH AND CLINICAL PRACTICE

Adequate sleep duration accentuates the effect of glucagon-like peptide-1 receptor variant on HbA1c: A gene-environment interaction study

Article

作者: Wu, Hanzhang ; Chen, Wei ; Wang, Ningjian ; Wei, Jiahe ; Tan, Xiao ; Benedict, Christian ; Zheng, Ying

BACKGROUND:

Both glucagon-like peptide-1 receptor (GLP1R) agonists and lifestyle modifications are widely adopted in managing glycemia. However, the joint effects of GLP1R agonists with lifestyle on glycemic traits have not been evaluated.

METHODS:

This gene-environment study tested the interaction between GLP1R-rs10305492 variant, consistent with the effect of GLP1R agonist therapies, and four lifestyle factors (diet, physical activity, sleep duration, and chronotype) for glucose and glycated hemoglobin (HbA1c) levels among 263,846 UK Biobank participants. Linear regression models were conducted to evaluate the effects of the rs10305492 and lifestyle factors on glucose and HbA1c levels.

RESULTS:

GLP1R-rs10305492-AA/AG genotype combined a healthy diet, regular physical activity, adequate sleep duration, or morning chronotype were associated with lower glucose and HbA1c levels (all P for trend < 0.001). A synergistic effect was found between rs10305492 and sleep duration on HbA1c, suggesting a recommended adequate sleep duration (7-8 h/day) may amplify the HbA1c lowering effect of GLP1R agonists. Joint effects of the rs10305492 and adequate sleep were associated with a 26 % reduced risk of hyperglycemia (>7.8 mmol/L) risk and a 22 % lower of high HbA1c (>39 mmol/mol or 5.7 %).

CONCLUSIONS:

Combining GLP1R agonists with adequate sleep may provide additional benefits for glycemic control in clinical practice.

2024-10-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Targeting microglial GLP1R in epilepsy: A novel approach to modulate neuroinflammation and neuronal apoptosis

Article

作者: Du, Liangchao ; Zhang, Kai ; Wang, Xiaoyue ; He, Xinghui ; Fu, Shiyu ; Zhou, Yu ; Liu, Dingyang ; Yang, Zhuanyi ; Yang, Zhiquan

BACKGROUND:

Epilepsy is a prevalent disorder of the central nervous system. Approximately, one-third of patients show resistance to pharmacological interventions. The pathogenesis of epilepsy is complex, and neuronal apoptosis plays a critical role. Aberrantly reactive astrocytes, induced by cytokine release from activated microglia, may lead to neuronal apoptosis. This study investigated the role of glucagon-like peptide 1 receptor (GLP1R) in microglial activation in epilepsy and its impact on astrocyte-mediated neurotoxicity.

METHODS:

We used human hippocampal tissue from patients with temporal lobe epilepsy and a pilocarpine-induced epileptic mouse model to assess neurobiological changes in epilepsy. BV2 microglial cells and primary astrocytes were used to evaluate cytokine release and astrocyte activation in vitro. The involvement of GLP1R was explored using the GLP1R agonist, Exendin-4 (Ex-4).

RESULTS:

Our findings indicated that reduced GLP1R expression in hippocampal microglia in both epileptic mouse models and human patients, correlated with increased cytokine release and astrocyte activation. Ex-4 treatment restored microglial homeostasis, decreased cytokine secretion, and reduced astrocyte activation, particularly of the A1 phenotype. These changes were associated with a reduction in neuronal apoptosis. In addition, Ex-4 treatment significantly decreased the frequency and duration of seizures in epileptic mice.

CONCLUSIONS:

This study highlights the crucial role of microglial GLP1R in epilepsy pathophysiology. GLP1R downregulation contributes to microglial- and astrocyte-mediated neurotoxicity, exacerbating neuronal death and seizures. Activation of GLP1R with Ex-4 has emerged as a promising therapeutic strategy to reduce neuroinflammation, protect neuronal cells, and control seizures in epilepsy. This study provides a foundation for developing novel antiepileptic therapies targeting microglial GLP1R, with the potential to improve outcomes in patients with epilepsy.

2024-02-01·Diabetes

Leptin Reduction as a Required Component for Weight Loss

Article

作者: An, Zhiqiang ; He, Sijia ; Han, Xianlin ; Li, Na ; Zhang, Ningyang ; Wang, May-Yun ; Li, Guannan ; Zhu, Yi ; Xiong, Wei ; Zhang, Zhuzhen ; Zhu, Qingzhang ; Scherer, Philipp E. ; Ikejiofor, Christian ; Zhao, Shangang ; Jiang, Nisi ; Solis-Herrera, Carolina ; Elmquist, Joel K. ; Kusminski, Christine

Article Highlights:

100 项与 GLP1R Agonist(AVVA) 相关的药物交易

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