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Additional bioanalytical, dose analysis and DSMB costs for PTI-125 development

PTI-125 开发的额外生物分析、剂量分析和 DSMB 成本

基本信息

批准号：
9524402
负责人：
Lindsay H Burns
金额：
$ 14.17万
依托单位：
CASSAVA SCIENCES, INC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9524402
关键词：
Administrative Supplement Affinity Age Alzheimer&apos s Disease Amyloid Autopsy Binding Biodistribution Biological Availability Blood Blood Pressure Canis familiaris Chemistry Chronic Clinical Clinical Trials Clinical Trials Data Monitoring Committees Data Deposition Development Disease Documentation Dose Drug or chemical Tissue Distribution Electrocardiogram Employee Enrollment Female Frequencies Functional disorder Goals Grant Heart Rate Hematology Hepatocyte Human Human Resources Impairment Inflammation Inflammatory Insulin Receptor Label Methods Modification Molecular Conformation Mus Neurofibrillary Tangles Nicotinic Receptors No-Observed-Adverse-Effect Level Oral Pathologic Patients Pharmaceutical Preparations Pharmacology Study Phase Phenotype Placebos Plasma Rattus Recovery Recruitment Activity Regulation Reporting Safety Sampling Scaffolding Protein Shapes Signal Transduction Site Small Business Innovation Research Grant Synaptic plasticity TLR4 gene Testing Therapeutic Time Toxic effect Toxicology Urinalysis Urine Validation Work alpha-bungarotoxin receptor base brain tissue clinical development clinical lot cognitive function cost cytokine efficacy study exposed human population filamin healthy volunteer improved male metabolic profile mouse model neuroinflammation novel novel strategies preclinical study prevent receptor respiratory safety study small molecule symptomatic improvement synaptic function tau Proteins therapeutic candidate volunteer

项目摘要

PTI-125 is a novel small molecule AD therapeutic candidate with a novel target and mechanism of action. PTI-125 binds and reverses an altered conformation of the scaffolding protein filamin A (FLNA) to prevent Aβ42’s tight binding to and toxic signaling via the α7-nicotinic acetylcholine receptor (α7nAChR) as well as Aβ42’s aberrant activation of toll-like receptor 4 (TLR4). Hence, by restoring FLNA’s native shape and blocking these two toxic cascades, PTI-125 reduces both tau hyperphosphorylation and neuroinflammation. Downstream effects include reduced neurofibrillary lesions and amyloid deposits, suggesting disease modification, and improved synaptic plasticity and function of α7nAChR, NMDAR and insulin receptors, suggesting symptomatic improvement. We will pursue a label claim of symptomatic improvement instead of the more difficult claim of disease modification. An IND has been filed and the first-inhuman trial will start August 9, 2017. The current administrative supplement proposal includes additional development work related to this first-in-human clinical trial and the ongoing interim 3-month oral toxicity study in dog. These activities include 1) the Data and Safety Monitoring Board, 2) the bioanalytical method adaptation and validation for use in human plasma, 3) the bioanalysis of plasma samples from the 3-month dog study, 4) the dose analysis for the dosing solutions used in the 3-month dog study, required by GLP regulations, and 5) the cost of the recently completed independent audit of the previous SBIR grant that closed Dec. 31, 2016. All these activities are necessary for the continued development of this novel AD therapeutic candidate.

PTI-125是一种新的小分子阿尔茨海默病治疗候选药物，具有新的靶点和靶点