A Novel Anti-inflammatory and Anti-oxidant Therapy for Treating Non-healing Diabetic Foot Ulcers

一种治疗不愈合糖尿病足溃疡的新型抗炎和抗氧化疗法

基本信息

  • 批准号:
    10600900
  • 负责人:
  • 金额:
    $ 29.92万
  • 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
  • 起止时间:
    2022-09-17 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Delayed or impaired wound healing is a serious complication of diabetes, often leading to lower limb ampu- tations. By 2050, 1 in 3 Americans will develop diabetes, and up to 34% of diabetic patients will develop a diabetic foot ulcer (DFU) in their lifetime. Standard of care for DFUs includes debridement, infection control, maintaining a moist wound environment, and pressure offloading. Despite these interventions, a large number of DFUs fail to heal and are associated with a cost that exceeds $31 billion annually. Chronic inflammation and increased oxidative stress have been implicated in the pathogenesis of the diabetic wound healing impairment. We have designed and tested a new therapeutic that synergistically targets both inflammation and oxidative stress using novel cerium oxide nanoparticles (CNP), which possess reactive oxygen species (ROS) scavenging properties, conjugated with an anti-inflammatory microRNA mimic (miR146a) that is deficient in diabetic wounds and inhibits the activation of NF-kappa-B-induced pro-inflammatory response. Importantly, our novel, patented conjugate CNP-miR146a efficiently delivers miR146a into the wound and reduces inflammation and ROS. Using a CNP-miR146a specifically formulated for intradermal injection (CTX-001), we demonstrated that a one-time administration of CTX-001 to full-thickness wounds fully corrected the wound healing impairment in diabetic mice and elicited a significant 25% improvement in wounds in diabetic pigs. Repeated weekly admin- istration corrected the diabetic wound healing impairment in diabetic pigs, similar to healing in non-diabetic wounds. We have subsequently developed CNP-mi146a as a hydroxymethylcellulose gel formulation (CTX-004), which can be used for topical administration as a more attractive alternative based on market research. The main objective of this Phase I application by Ceria Therapeutics is to optimize the gel formulation of CTX-004 (Aim 1.1) and demonstrate its efficacy in the treatment of diabetic mouse wounds by establishing the minimum effective dose required to improve the time to and quality of wound healing (Aim 1.2). In Aim 2 we will perform a preclinical study to compare the efficacy of the optimal formulation and dose of CTX-004 with the only FDA approved gel (Regranex®) for treating diabetic foot ulcers. Aim 3 will assess if there is any effect of bacterial load on the efficacy of CTX-004 in the healing of diabetic mouse wounds. Successful completion of the efforts de- scribed in this proposal will position Ceria to advance CTX-004 to IND-enabling studies, file an IND application, and initiate a First-in-Human clinical trial.
项目摘要 伤口愈合延迟或受损是糖尿病的严重并发症,通常导致下肢截肢。 站。到2050年,1/3的美国人将患糖尿病,高达34%的糖尿病患者将患糖尿病。 足部溃疡(DFU)。DFU的标准护理包括清创、感染控制、维护 潮湿的伤口环境和压力卸载。尽管采取了这些干预措施,但大量DFU还是失败了 每年的治疗费用超过310亿美元。慢性炎症和增加 氧化应激与糖尿病伤口愈合障碍的发病机制有关。我们有 设计并测试了一种新的治疗方法,该方法使用 新型氧化铈纳米颗粒(CNP),其具有活性氧(ROS)清除性质, 与抗炎microRNA模拟物(miR 146 a)缀合,所述miR 146 a在糖尿病伤口中缺乏并抑制 NF-κ B诱导的促炎反应的激活。重要的是,我们的新型专利结合物 CNP-miR 146 a有效地将miR 146 a递送到伤口中并减少炎症和ROS。 使用专门配制用于皮内注射的CNP-miR 146 a(CTX-001),我们证明了 CTX-001对全层伤口的一次性给药完全纠正了 在糖尿病小鼠中的伤口得到了显著的25%的改善。每周重复给药- 治疗纠正了糖尿病猪的糖尿病伤口愈合障碍,与非糖尿病猪的愈合相似 伤口 我们随后开发了CNP-mi 146 a作为羟甲基纤维素凝胶制剂(CTX-004), 其可用于局部给药,作为基于市场研究的更有吸引力的替代方案。的 Ceria Therapeutics公司的这一I期申请的主要目的是优化CTX-004的凝胶制剂 (Aim 1.1),并通过建立最小的 改善伤口愈合时间和质量所需的有效剂量(目标1.2)。在目标2中,我们将执行 临床前研究,以比较CTX-004的最佳制剂和剂量与唯一FDA 批准的凝胶(Regranex®)用于治疗糖尿病足溃疡。目标3将评估细菌负荷是否有任何影响 CTX-004在糖尿病小鼠伤口愈合中的功效。圆满完成了各项工作, 本提案中所述的内容将使Ceria能够推进CTX-004的IND研究,提交IND申请, 并启动首次人体临床试验

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

David Jackson其他文献

David Jackson的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('David Jackson', 18)}}的其他基金

Targeting inflammation and oxidative stress to treat acute lung injury with CNP-miR146a
利用 CNP-miR146a 靶向炎症和氧化应激治疗急性肺损伤
  • 批准号:
    10382076
  • 财政年份:
    2022
  • 资助金额:
    $ 29.92万
  • 项目类别:
Targeting inflammation and oxidative stress to treat acute lung injury with CNP-miR146a
利用 CNP-miR146a 靶向炎症和氧化应激治疗急性肺损伤
  • 批准号:
    10758905
  • 财政年份:
    2022
  • 资助金额:
    $ 29.92万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 29.92万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了