Therapeutic antibody for anorexia nervosa

神经性厌食症的治疗性抗体

• 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
• 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

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性抗体 摘要 神经性厌食症（AN）是一种精神疾病，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%，最高可达85%。自然的过程是 可变的，长期死亡率是任何精神疾病中最高的。治疗依赖于营养 和心理治疗，并没有具体的药物治疗已确定为AN。生长分化因子15 GDF 15作为体重减轻的关键介质被充分记录，并且高GDF 15水平与体重减轻相关。 名为. GDF 15的施用导致小鼠、大鼠和灵长类动物的体重减轻。我们发现了一个高- 在肿瘤相关恶病质的动物模型中中和GDF 15的亲和人单克隆抗体。 在该I期项目期间，我们将在AN的鼠模型中证明该抗体的活性。2期研究 将推进临床前测试，包括药代动力学和毒理学，为IND做准备。 该项目开发的治疗性抗体将直接阻断导致体重减轻的主要原因，以改善 AN患者的生活质量。