Diversification of Glomerular Kidney Disease Treatments By Targeting Therapeutics to the Kidney

通过针对肾脏的治疗来实现肾小球肾病治疗的多样化

基本信息

  • 批准号:
    10808617
  • 负责人:
  • 金额:
    $ 36.79万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-22 至 2025-09-14
  • 项目状态:
    未结题

项目摘要

ABSTRACT Novel approaches to the treatment of glomerular kidney diseases are needed given that they represent the third most common cause of end stage renal disease. Systemic lupus erythematosus induced kidney disease (SLEN) is one glomerular disease where up to 60% of patients exhibit significant declines in kidney function, resulting in end stage renal disease in ~20%. Although novel treatments are being explored for lupus, they generally do not benefit the majority of patients and cause systemic immunosuppression, leaving the majority of the population with less effective treatment options. Additionally, neither new nor old treatments have been evaluated for their ability to target to the kidney and achieve sufficient exposure to influence the localized disease processes. The development of novel and effective renal targeted treatment approaches for glomerular kidney diseases, including SLEN, are needed to meet the clinical efficacy and safety needs of patients with these disorders. We have recently published research for enhanced kidney deposition of imatinib in a murine model of SLEN, when formulated in a nanoemulsion developed to optimize kidney exposure. Results from our studies showed three-fold higher kidney deposition of imatinib in MRL/MpJ-Faslpr mice that received our novel nanoformulation vs. free drug. We will now test the novel imatinib formulation after chronic dosing to evaluate efficacy and safety in two mouse models of SLEN. We will also modify this formulation by linking a relevant ligand or an antibody fragment to target a receptor and protein, respectively, that are upregulated in glomerular mesangial cells in SLEN. We will test whether these formulation techniques applied to the existing nanoemulsion will enhance imatinib glomerular deposition and retention, improve selectivity for targeting mesangial cells, improve therapeutic efficacy and provide relative safety, as compared to our primary formulation. The central hypotheses of our research are that 1) promising SLEN treatments can be formulated to enhance delivery to the diseased kidney and targeted structures, and 2) animal models that represent human SLEN will demonstrate favorable treatment responses, pharmacokinetics, and enhanced safety with imatinib nanoformulations vs. free drug. The research team comprised of scientists with diverse backgrounds in glomerular kidney diseases, drug development, nanoformulations, toxicology, and renal pathology across schools at the University of Colorado Anschutz Medical Center, will synergize their efforts to successfully develop novel strategies to enhance kidney delivery and accumulation of therapeutics for the treatment of glomerular kidney diseases.
摘要

项目成果

期刊论文数量(0)
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MELANIE S JOY其他文献

MELANIE S JOY的其他文献

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{{ truncateString('MELANIE S JOY', 18)}}的其他基金

Drug Metabolizing Enzyme and Transporter Function in Chronic Kidney Disease
慢性肾病的药物代谢酶和转运蛋白功能
  • 批准号:
    8759210
  • 财政年份:
    2014
  • 资助金额:
    $ 36.79万
  • 项目类别:
Drug Metabolizing Enzyme and Transporter Function in Chronic Kidney Disease
慢性肾病的药物代谢酶和转运蛋白功能
  • 批准号:
    9329438
  • 财政年份:
    2014
  • 资助金额:
    $ 36.79万
  • 项目类别:
Drug Metabolizing Enzyme and Transporter Function in Chronic Kidney Disease
慢性肾病的药物代谢酶和转运蛋白功能
  • 批准号:
    9144405
  • 财政年份:
    2014
  • 资助金额:
    $ 36.79万
  • 项目类别:
PHARMACOGENIC REASONS FOR POOR LUPUS NEPHRITIS OUTCOMES
狼疮性肾炎预后不良的药理学原因
  • 批准号:
    7716807
  • 财政年份:
    2008
  • 资助金额:
    $ 36.79万
  • 项目类别:
P-GLYCOPROTEIN AND CYTOCHROME P450 GENOTYPE AND PHENOTYPE ON RESPONSE TO ANCA
P-糖蛋白和细胞色素 P450 基因型和表型对 ANCA 的反应
  • 批准号:
    7716797
  • 财政年份:
    2008
  • 资助金额:
    $ 36.79万
  • 项目类别:
P-GLYCOPROTEIN AND CYTOCHROME P450 GENOTYPE AND PHENOTYPE ON RESPONSE TO ANCA
P-糖蛋白和细胞色素 P450 基因型和表型对 ANCA 的反应
  • 批准号:
    7625574
  • 财政年份:
    2006
  • 资助金额:
    $ 36.79万
  • 项目类别:
PHARMACOGENIC REASONS FOR POOR LUPUS NEPHRITIS OUTCOMES
狼疮性肾炎预后不良的药理学原因
  • 批准号:
    7625587
  • 财政年份:
    2006
  • 资助金额:
    $ 36.79万
  • 项目类别:
PHARMACOGENIC REASONS FOR POOR LUPUS NEPHRITIS OUTCOMES
狼疮性肾炎预后不良的药理学原因
  • 批准号:
    7377537
  • 财政年份:
    2005
  • 资助金额:
    $ 36.79万
  • 项目类别:
P-GLYCOPROTEIN AND CYTOCHROME P450 GENOTYPE AND PHENOTYPE ON RESPONSE TO ANCA
P-糖蛋白和细胞色素 P450 基因型和表型对 ANCA 的反应
  • 批准号:
    7377524
  • 财政年份:
    2005
  • 资助金额:
    $ 36.79万
  • 项目类别:
Pharmacokinetics & Genomics in Glomerular Diseases
药代动力学
  • 批准号:
    7111085
  • 财政年份:
    2004
  • 资助金额:
    $ 36.79万
  • 项目类别:

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