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
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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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