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Novel Therapeutic Approaches for NPC Disease

鼻咽癌的新治疗方法

基本信息

批准号：
10650430
负责人：
Vinay Aakalu
金额：
$ 57.56万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
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：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10650430
关键词：
Address Affect Anti-Bacterial Agents Antifungal Agents Biochemical Biochemistry Biological Markers Cell Culture Techniques Cell model Cells Central Nervous System Cholesterol Chronic Clinical DNA Sequence Alteration Data Defect Diagnosis Disease Dose Drug Design Drug Kinetics Epithelium Exhibits FDA approved Fibroblasts Foundations Functional disorder Gangliosides Genes Genetic Genetic Models Human Impairment In Vitro Ligands Lipids Liver Longevity Lysosomes Mass Spectrum Analysis Measures Methods Modeling Molecular Biology Techniques Mus Mutation NPC1 gene Nature Neimann-Pick&apos s Disease Type C Nerve Degeneration Neurons Niemann-Pick Diseases Pathway interactions Patients Peptides Peripheral Phenotype Point Mutation Positioning Attribute Predisposition Protein Family Proteins Regulation Reporting Role Splenomegaly Testing Therapeutic Translating Treatment Effectiveness Work autosome burden of illness cell type cholesterol trafficking clinical phenotype disease phenotype drug metabolism efficacy study emerging adult histatin 1 histidine-rich proteins immunogenicity immunoregulation in vivo mouse model mutant neuronal survival novel strategies novel therapeutic intervention novel therapeutics patient population pharmacokinetics and pharmacodynamics pharmacologic polypeptide prototype receptor reduce symptoms sigma-2 receptor treatment strategy

项目摘要

PROJECT SUMMARY/ABSTRACT Niemann-Pick disease, type C1 (NPC1), is an autosomal recessive, neurovisceral disorder, and patients typically succumb to complications of the disease in the early adulthood years. The clinical phenotype of NPC1 is broad including both central nervous system and peripheral dysfunction and currently there is no FDA- approved therapy. The enclosed proposal seeks to develop and understand the mechanism of action of a new class of peptides to ameliorate cholesterol storage and associated phenotypes of NPC1. Our central approach is to address the biochemical deficits upstream of the NPC1 protein. First, we will understand how defined protein and lipid biomarkers respond to peptide treatment. Second, we will perform a DMPK study and investigate lifespan extension with treatment. Third, we will investigate the mechanism of action by which these peptides reduce cholesterol storage. To carry out the proposed project, we will leverage our expertise in mass spectrometry, biochemistry and molecular biology techniques.

项目摘要/摘要 Niemann-Pick病，C1型(NPC1)，是一种常染色体隐性遗传的神经内脏疾病，患者通常在成年初期死于疾病的并发症。NPC1的临床表型广泛包括中枢神经系统和外周功能障碍，目前没有FDA- 批准的治疗方法。所附提案旨在开发和理解新的一类用于改善胆固醇储存和NPC1相关表型的多肽。我们的中心方法是为了解决NPC1蛋白上游的生化缺陷。首先，我们将了解如何定义蛋白质和脂肪生物标记物对多肽治疗有反应。第二，我们将进行DMPK研究，并研究如何通过治疗延长寿命。第三，我们将研究其作用机制。这些多肽可以减少胆固醇的储存。为推行建议中的计划，我们会利用我们的专业知识质谱学、生物化学和分子生物学技术。