Therapeutic antibody for anorexia nervosa

神经性厌食症的治疗性抗体

基本信息

批准号：
10480127
负责人：
JAMES W LARRICK
金额：
$ 25.96万
依托单位：
LARIX BIOSCIENCE, LLC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10480127
关键词：
Affect Affinity Amygdaloid structure Animal Model Animals Anorexia Anorexia Nervosa Antibodies Binding Body Weight Body Weight decreased Brain Stem Cachexia Clinical Complex Data Desire for food Development Diet Habits Dose Drug Kinetics Eating Eating Disorders Food Energy GDF15 gene Genetic Models Half-Life Homeostasis Hypothalamic structure Laboratories Lateral Lead Mediator of activation protein Mental disorders Modeling Modification Monoclonal Antibodies Mus Neurons Nucleus solitarius Nutritional Nutritional Support Outcome Pathway interactions Patients Pharmaceutical Preparations Pharmacotherapy Phase Phosphorylation Plasma Population Preclinical Testing Preparation Primates Psychiatric therapeutic procedure Psychotherapy Quality of life Rattus Safety Signal Transduction Structure of area postrema Therapeutic Therapeutic Monoclonal Antibodies Therapeutic antibodies Time Toxic effect Toxicology Weight Gain Work Xenograft procedure assay development base cancer cachexia energy balance human monoclonal antibodies immunogenicity improved in vitro activity in vivo mortality mouse model neuronal circuitry neutralizing monoclonal antibodies parabrachial nucleus phase 2 study pre-clinical prevent receptor relating to nervous system targeted treatment tumor

项目摘要

Therapeutic antibody for anorexia nervosa Abstract Anorexia nervosa (AN) is a psychiatric condition characterized by changes in eating habits eventually leading to weight loss of more than 15% and up to 85% in comparison to a healthy population. The natural course is variable, and long-term mortality is one of the highest of any psychiatric disorder. Treatment relies on nutritional and psychotherapy, and no specific drug treatment has been identified for AN. Growth differentiation factor 15 (GDF15) is well documented as a critical mediator of body weight loss, and high GDF15 levels are associated with AN. Administration of GDF15 causes weight loss in mice, rats, and primates. We have identified a high- affinity human monoclonal antibody that neutralizes GDF15 in animal models of tumor-associated cachexia. During this Phase 1 project, we will demonstrate activity of this antibody in murine models of AN. Phase 2 studies will advance preclinical testing, including pharmacokinetics and toxicology, in preparation for an IND. The therapeutic antibody to be developed in this project will directly block a major cause of weight loss to improve quality of life in AN patients.

神经性厌食症的治疗抗体抽象的神经性厌食症（AN）是一种精神病，其特征是饮食习惯的改变，最终导致与健康人群相比，体重减轻超过15％，多达85％。自然的路线是可变和长期死亡率是任何精神病中最高的死亡率之一。治疗依赖营养和心理疗法，尚未确定An的特定药物治疗。生长分化因子15 （GDF15）被充分记录为体重减轻的关键调解人，高GDF15水平与与GDF15的给药会导致小鼠，大鼠和灵长类动物的体重减轻。我们已经确定了一个高亲和力的人类单克隆抗体中和在与肿瘤相关的卡氏症动物模型中中和GDF15。在此阶段1项目中，我们将在An的鼠模型中证明该抗体的活性。第2阶段研究将推进包括药代动力学和毒理学在内的临床前测试，为IND做准备。这该项目中要开发的治疗抗体将直接阻止体重减轻的主要原因以改善患者的生活质量。