Therapeutic antibody for anorexia nervosa
Therapeutic antibody for anorexia nervosa
批准号:
10480127
负责人:
JAMES W LARRICK
金额:
$25.96万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-03-01 至 2024-02-29
关键词:
AffectAffinityAmygdaloid structureAnimal ModelAnimalsAnorexiaAnorexia NervosaAntibodiesBindingBody WeightBody Weight decreasedBrain StemCachexiaClinicalComplexDataDesire for foodDevelopmentDiet HabitsDoseDrug KineticsEatingEating DisordersFood EnergyGDF15 geneGenetic ModelsHalf-LifeHomeostasisHypothalamic structureLaboratoriesLateralLeadMediator of activation proteinMental disordersModelingModificationMonoclonal AntibodiesMusNeuronsNucleus solitariusNutritionalNutritional SupportOutcomePathway interactionsPatientsPharmaceutical PreparationsPharmacotherapyPhasePhosphorylationPlasmaPopulationPreclinical TestingPreparationPrimatesPsychiatric therapeutic procedurePsychotherapyQuality of lifeRattusSafetySignal TransductionStructure of area postremaTherapeuticTherapeutic Monoclonal AntibodiesTherapeutic antibodiesTimeToxic effectToxicologyWeight GainWorkXenograft procedureassay developmentbasecancer cachexiaenergy balancehuman monoclonal antibodiesimmunogenicityimprovedin vitro activityin vivomortalitymouse modelneuronal circuitryneutralizing monoclonal antibodiesparabrachial nucleusphase 2 studypre-clinicalpreventreceptorrelating to nervous systemtargeted treatmenttumor
中文摘要
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。
本项目拟开发的治疗性抗体将直接阻断改善减肥的一个主要原因
AN患者的生活质量。
英文摘要
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.
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