SMART HAND

智能手

基本信息

项目摘要

DESCRIPTION (provided by applicant): This shared investigator R01 is an extension of 5 P01 NS043985-09. The current work builds on prior successes in developing long-acting nanoformulated antiretroviral therapies (nanoART) to improve drug delivery and therapeutic outcomes for aged virus-infected people. Elucidating the interplay between aging, HIV disease and ART is the overarching project goal. The tools are available to address this interplay which can simplify drug regimens and improve disease outcomes. First, nanoART is available for long- term testing of antiretroviral responses together with central nervous system (CNS) and broad metabolic functions. Second, interdisciplinary bioimaging, behavior, and nanopharmaceutics can evaluate virus, drug, immune, and age-related toxicities. Third, drug pharmacokinetic, pharmacodynamics, drug-drug interactions can be measured by employing PXR humanization (the androstane receptor with replacement of the mouse Cyp3a with human CYP3A4) in rodents. This can be used to evaluate long-term immune and antiviral responses. Fourth, a novel tool designed to improve ART delivery to viral reservoirs was discovered for theranostics (simultaneous diagnostics and therapeutics). This system is called small magnetite ART (or SMART) and permits assay of drug biodistribution by imaging tests. Such outcome measures would improve ART CNS and lymphoid delivery and thus combat persistent HIV-1 infection. A group of investigators with productive histories of working together was assembled. They include neuroscientists (H. Gendelman, Co- PI), immunopathologists (L. Poluektova, Co-PI), aging and cognitive behavior researchers (S. Bonasera), bioimaging experts (M. Boska) those with expertise in neurodegenerative diseases (R. L. Mosley), and experts in nanomedicine and drug delivery (X. Liu). The work is timely and relevant. Although ART has profoundly reduced morbidities and mortality for HIV infection coincident with virus reductions and immune preservation, the prevalence of neurocognitive impairments and drug toxicities remain common. Indeed, the doubling of virus-infected patients > 50 years of age is upon us. New co-morbid conditions now include cerebrovascular disease, non-AIDS malignancies, insulin resistance, hyperlipidemia, dementia, and liver, renal and bone disorders. This demands new model systems for disease studies relevant to current HIV/AIDS trends. Indeed, the work reflects the changing epidemiologic patterns of human disease. [We acknowledge that the prior submission lacked preliminary data and details about our humanized brain model and nanoformulations and response of the animals to treatments. A number of recent publications and significant new preliminary data are now included that addresses each of these concerns in a thorough and reasoned manner.] The tools that are needed to tackle relevant questions in HIV and aging are also available for study.
描述(由申请人提供):该共享研究者R 01是5 P01 NS 043985 -09的扩展。目前的工作建立在开发长效纳米抗逆转录病毒疗法(nanoART)的成功基础上,以改善老年病毒感染者的药物输送和治疗效果。阐明老龄化、艾滋病毒疾病和抗逆转录病毒疗法之间的相互作用是该项目的总体目标。这些工具可用于解决这种相互作用,从而简化药物治疗方案并改善疾病结果。首先,nanoART可用于抗逆转录病毒反应以及中枢神经系统(CNS)和广泛代谢功能的长期测试。其次,跨学科的生物成像,行为和纳米药剂学可以评估病毒,药物,免疫和年龄相关的毒性。第三,药物药代动力学、药效学、药物-药物相互作用可以通过在啮齿动物中采用PXR人源化(用人CYP 3A 4替换小鼠Cyp 3a的雄烷受体)来测量。这可用于评估长期免疫和抗病毒反应。第四,发现了一种用于治疗诊断学(同时诊断和治疗)的新工具,旨在改善ART向病毒储库的递送。该系统被称为小磁铁矿ART(或SMART),并允许通过成像试验测定药物的生物分布。这些结果措施将改善ART CNS和淋巴传递,从而对抗持续的HIV-1感染。一组有着合作历史的调查人员聚集在一起。他们包括神经科学家(H。Gendelman,Co-PI),免疫病理学家(L. Poluektova,Co-PI),衰老和认知行为研究人员(S。Bonasera),生物成像专家(M.博斯卡)那些在神经退行性疾病(R。L.莫斯利),以及纳米医学和药物输送专家(X。Liu).这项工作是及时和相关的。虽然ART大大降低了HIV感染的发病率和死亡率,同时减少了病毒和免疫保护,但神经认知障碍和药物毒性的患病率仍然很常见。事实上,50岁以上的病毒感染患者人数翻了一番。新的合并症现在包括脑血管疾病、非艾滋病恶性肿瘤、胰岛素抵抗、高脂血症、痴呆以及肝、肾和骨疾病。这就要求建立与当前艾滋病毒/艾滋病趋势相关的疾病研究新模式系统。事实上,这项工作反映了人类疾病不断变化的流行病学模式。[We我们承认,之前提交的材料缺乏关于我们的人源化大脑模型和纳米制剂以及动物对治疗的反应的初步数据和细节。现在包括一些最近的出版物和重要的新的初步数据,以彻底和合理的方式解决这些问题。解决艾滋病毒和老龄化相关问题所需的工具也可供研究。

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(6)

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 }}

Howard E Gendelman其他文献

HIV-1 hijacks tunneling nanotubes and secretory microvesicles for intercellular spread in monocyte-derived macrophages
  • DOI:
    10.1186/1742-4690-6-s2-o22
  • 发表时间:
    2009-09-24
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Irena Kadiu;Jan M Orenstein;Howard E Gendelman
  • 通讯作者:
    Howard E Gendelman

Howard E Gendelman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('Howard E Gendelman', 18)}}的其他基金

HIV-1DetectionandEliminationFrom CNS Mononuclear Phagocytes
CNS 单核吞噬细胞中 HIV-1 的检测和消除
  • 批准号:
    10645139
  • 财政年份:
    2021
  • 资助金额:
    $ 62.58万
  • 项目类别:
HIV-1DetectionandEliminationFrom CNS Mononuclear Phagocytes
CNS 单核吞噬细胞中 HIV-1 的检测和消除
  • 批准号:
    10454408
  • 财政年份:
    2021
  • 资助金额:
    $ 62.58万
  • 项目类别:
HIV-1 Detection and Elimination From CNS Mononuclear Phagocytes
CNS 单核吞噬细胞中 HIV-1 的检测和消除
  • 批准号:
    10327550
  • 财政年份:
    2021
  • 资助金额:
    $ 62.58万
  • 项目类别:
Neuroimmunology of Disease Training Program
疾病神经免疫学培训计划
  • 批准号:
    10200159
  • 财政年份:
    2018
  • 资助金额:
    $ 62.58万
  • 项目类别:
Neuroimmunology of Disease Training Program
疾病神经免疫学培训计划
  • 批准号:
    10629027
  • 财政年份:
    2018
  • 资助金额:
    $ 62.58万
  • 项目类别:
Neuroimmunology of Disease Training Program
疾病神经免疫学培训计划
  • 批准号:
    10875267
  • 财政年份:
    2018
  • 资助金额:
    $ 62.58万
  • 项目类别:
Combined Molecular Excision Therapy (CMET) for Eliminating HIV-1
用于消除 HIV-1 的联合分子切除疗法 (CMET)
  • 批准号:
    10217975
  • 财政年份:
    2017
  • 资助金额:
    $ 62.58万
  • 项目类别:
Glutaminase and its neurotoxic link to HAND
谷氨酰胺酶及其与 HAND 的神经毒性联系
  • 批准号:
    9700732
  • 财政年份:
    2016
  • 资助金额:
    $ 62.58万
  • 项目类别:
SMART HAND
智能手
  • 批准号:
    8738559
  • 财政年份:
    2013
  • 资助金额:
    $ 62.58万
  • 项目类别:
Neuronanomedicine
神经纳米医学
  • 批准号:
    8529879
  • 财政年份:
    2013
  • 资助金额:
    $ 62.58万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了