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Development of a lead candidate for the treatment of Alzheimer's disease

开发治疗阿尔茨海默病的主要候选药物

基本信息

批准号：
10553082
负责人：
Corinne Ida Lasmezas
金额：
$ 39.07万
依托单位：
VOVA IDA THERAPEUTICS INC
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：
2022-09-30 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10553082
关键词：
Affect Affinity Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease patient Area Behavioral Binding Biochemical Biological Assay Biological Availability Biological Markers Blood Circulation Brain Cause of Death Cell Survival Cell surface Cells Complex Cytochrome P450 Degradation Pathway Depressed mood Development Disease Dose Drug Kinetics Drug Targeting Enzymes Epidemic Evaluation Event Exposure to Florida Functional disorder G-Protein-Coupled Receptors Goals Half-Life Health Human Hydrogen Bonding In Vitro Intellectual Property Ion Channel Knock-in Lead Liver Microsomes Mediator of activation protein Membrane Proteins Memory Metabolic Monitor Mus Neurons Oral Oxidative Stress Pathogenicity Pathology Patients Penetration Peptides Permeability Persons Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacology Phase Phosphorylation Phosphotransferases Plasma Positioning Attribute PrP Property Protein Isoforms Rodent Safety Series Signal Transduction Societies Specificity Structure-Activity Relationship Surface Symptoms Synapses Testing Therapeutic Therapeutic Intervention Toxic effect United States Work age related neurodegeneration analog base bioinformatics tool chemical synthesis clinical development drug metabolism excitotoxicity high throughput screening immunocytochemistry improved in silico in vivo induced pluripotent stem cell lead candidate lead optimization mitochondrial dysfunction neuroblastoma cell neurotoxic novel novel lead compound novel therapeutic intervention preclinical development presenilin-1 receptor response screening panel small molecule targeted treatment tau Proteins therapeutic evaluation

项目摘要

SUMMARY Alzheimer’s disease (AD) is an age-related neurodegenerative disease that has become a global epidemic with over 40 million people affected worldwide and a projected 115 million in 2050. It is the 6th leading cause of death in the United States. AD has a tremendous impact on health, society and the economy. Approved treatments at best partially ameliorate some symptoms. There is an urgent need for novel, disease-modifying treatments. AD is a complex disease with multiple players that may be targeted for therapeutic intervention. A core pathogenic mechanism is the cellular toxicity of Ab42 peptide oligomers with the cascade of activation and phosphorylation events that follow neuronal oligomeric Ab42 binding and internalization. These result, inter alia, in oxidative stress, mitochondrial dysfunction, synaptic dysfunction, abnormal Ca2+ signaling and excitotoxicity. The overarching goal of this project is to develop a drug targeting neurotoxic Ab42 signaling. In this phase 1 component of the project, we will demonstrate the feasibility of optimizing our candidate compound into a therapeutic lead. We will conduct several rounds of structure-activity relationship studies aimed at increasing the compound’s potency, selectivity, metabolic and pharmacokinetic properties, including brain penetration. A series of in vitro/cell-based assays, DMPK studies and testing in a murine AD model will guide compound progression. The successful completion of phase 1 will deliver an optimized lead compound ready for development and IND-enabling studies in phase 2.

总结