HTORR Ocular Tissue Resource for Alzheimer's Disease Research

用于阿尔茨海默病研究的 HTORR 眼组织资源

• 批准号: 10284285
• 负责人: Thomas J Bell
• 金额: $ 33.44万
• 依托单位: NATIONAL DISEASE RESEARCH INTERCHANGE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-09 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10284285
• 关键词: Address; Administrative Supplement; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Award; Awareness; Biomedical Research; Brain imaging; Caregivers; Clinic; Clinical Trials; Collection; Communities; Data; Dementia; Development; Diagnostic; Disease; Disease Progression; Early Diagnosis; Ensure; Functional disorder; Funding; Grant; Healthcare Systems; Human; Impaired cognition; Impairment; Industry; Intervention; Investigation; Methodology; Methods; Neurodegenerative Disorders; Neurologic; Ophthalmology; Organ; Parents; Pathogenesis; Pathologic; Patients; Play; Principal Investigator; Procedures; Process; Publications; Reproducibility; Research; Research Personnel; Research Priority; Resources; Retinal Degeneration; Scientific Advances and Accomplishments; Services; Shipping; Standardization; Therapeutic; Tissues; Translating; United States National Institutes of Health; Work; base; blood-based biomarker; cohort; detection method; early detection biomarkers; experience; human old age (65+); human tissue; improved; interest; ocular imaging; pre-clinical; preservation; programs; recruit; targeted biomarker; tissue resource; translational study; treatment strategy

Program Director/Principal Investigator (Bell, Thomas, J.): Project Summary: The development of effective diagnostics, treatments or cures for a wide range of diseases requires translational studies that are directly relevant to human pathophysiology. The use of human biospecimens plays a key role in accelerating scientific discoveries across the entire spectrum of biomedical research, including neurodegenerative diseases such as Alzheimer's disease and related dementias (AD/ADRD). Evidence from clinical trials suggests that preclinical interventions may be key to slowing AD/ADRD disease progression (Dehghani et al, 2018). However, this treatment strategy requires early detection, which highlights the need for improved diagnostics for AD/ADRD. While much progress has been made with brain imaging and blood-based biomarkers, the detection methods remain invasive and expensive. Ocular-based pathological changes represent a potential target for biomarker investigation. To further investigate the ocular pathogenesis in AD/ADRD, investigators require access to a unique human tissue resource that could provide rigorous, reproducible, and uniform collection of human ocular and neurological tissue from defined cohorts of healthy and AD/ADRD donors. Access to such a resource would be critical to ensuring consistent, predictive, and reproducible experimental results that could be translated to the clinic for AD/ADRD patients. The National Disease Research Interchange (NDRI) is a 501(c)(3), not-for-profit organization that remains at the forefront of coordinating biospecimen procurement to match the needs of advancing scientific experimental methodologies, and enabling cutting-edge research. For over 30 years, NDRI has received NIH funding for the parent award to this administrative supplement, the Human Tissue and Organs for Research Resource (HTORR) Grant Number: U42OD011158. NDRI is applying for the NOT-AG-20-034, Notice of Special Interest (NOSI) to expand its focus beyond the scope of HTORR to develop and implement the Ocular Tissue Resource for AD/ADRD Research (OTR-AD). For the current proposal to develop and implement the OTR-AD, NDRI will: 1) work with investigators and key stakeholders at NEI to identify high-priority ocular biospecimen needs to support AD/ADRD research, 2) screen, authorize, recover, and process ocular and other neurological biospecimens from eligible post mortem donors, and 3) distribute biospecimens to approved investigators and promote awareness of OTR-AD to recruit new investigators. In doing so, the biospecimen collection and preservation methods will be optimized to the experimental hypotheses and procedures for each ADBR study using NDRI's experience in coordinating standardized procurement, processing, preservation and shipping methods and maintaining industry best practices and standards regarding the donation of human tissue for research. The overall objective of the OTR-AD is to provide well-annotated ocular and neurological tissue from defined cohorts of healthy and AD/ADRD donors that are suitable to generate high-quality, reproducible data for scientific review and publication to meet the needs of investigators and support the advancement of AD/ADRD research. Relevance: As the most common cause of dementia, AD is a devastating, progressive neurodegenerative disease that affects an estimated 5.8 million Americans age 65 and over (Alzheimer's Association et al, 2020) and has a significant burden on the US healthcare system as well as caregivers. As of yet, there are no disease- modifying treatment options available for AD/ADRD patients, making this a high priority for the research community. Disappointing clinical trial results evaluating potential disease-modifying treatments in patients with AD/ADRD have shifted the therapeutic focus to preclinical intervention (Crous-Bou et al, 2017), which requires improved diagnostics. While significant advances continue to be made with the identification of blood-based biomarkers for AD/ADRD, a parallel approach could be the use of ocular imaging or other ocular biomarkers for early detection. The objective of this proposal is to provide ocular biospecimens from post mortem AD/ADRD donors, as well as non-diseased control donors for the Ocular Tissue Resource for AD/ADRD Research (OTR- AD) that are suitable to support critical lines of investigation that address key issues related to ocular pathogenesis in the disease. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

项目主任/首席调查员(托马斯·贝尔，J.)： 项目总结： 开发对多种疾病的有效诊断、治疗或治愈方法需要翻译 与人类病理生理学直接相关的研究。人类生物标本的使用起到了关键作用 在加速整个生物医学研究领域的科学发现方面，包括 神经退行性疾病，如阿尔茨海默病和相关痴呆(AD/ADRD)。证据来自 临床试验表明，临床前干预可能是减缓AD/ADRD疾病进展的关键 (Dehgani等人，2018年)。然而，这种治疗策略需要及早发现，这突出了需要 改进了对AD/ADRD的诊断。虽然在脑成像和血液检测方面取得了很大进展 生物标志物，检测方法仍然是侵入性的和昂贵的。眼部病变 是生物标志物研究的潜在靶点。目的：进一步探讨青光眼的发病机制。 AD/ADRD，调查人员需要访问一种独特的人体组织资源，该资源可以提供严格的， 可重现的、统一的人类眼和神经组织收集自确定的健康和 AD/ADRD捐助者。对此类资源的访问对于确保一致性、预测性和 实验结果重复性好，可用于AD/ADRD患者的临床治疗。《国家报》 疾病研究交换(NDRI)是一个501(C)(3)非营利性组织，它仍然处于 协调生物胺采购，以满足推进科学实验方法学的需要； 并使前沿研究成为可能。30多年来，NDRI一直获得NIH父母奖的资金，以 这一行政副刊，人体组织和器官研究资源(HTORR)的拨款编号： U42OD011158。NDRI正在申请NOT-AG-20-034，特别利益通知(NOSI)，以扩大其重点 超越HTORR范围为AD/ADRD研究开发和实施眼组织资源 (OTR-AD)。对于目前开发和实施OTR-AD的提议，NDRI将：1)与调查人员合作 以及NEI的主要利益相关者，以确定支持AD/ADRD研究的高优先级眼部生物肌肉注射需要， 2)从符合条件的尸检中筛选、授权、恢复和处理眼部和其他神经生物样本 捐赠者，以及3)向经批准的研究人员分发生物检疫剂，并提高对OTR-AD的认识以招募 新的调查员。 在此过程中，将优化生物样品的收集和保存方法，使其适合于实验 利用NDRI在协调标准化方面的经验进行每项ADBR研究的假设和程序 采购、加工、保存和运输方法以及维护行业最佳做法和 关于捐赠人体组织用于研究的标准。OTR-AD的总体目标是提供 来自确定的健康和AD/ADRD捐赠者队列的注释良好的眼和神经组织，这些捐赠者是 适用于生成高质量、可重现的数据，用于科学审查和出版，以满足 并支持推进AD/ADRD研究。 相关性：作为痴呆症最常见的原因，阿尔茨海默病是一种毁灭性的进行性神经退行性疾病 这种疾病影响着大约580万65岁及以上的美国人(阿尔茨海默氏症协会等人，2020年) 并对美国医疗体系和照顾者造成重大负担。到目前为止，还没有疾病- 修改AD/ADRD患者可用的治疗方案，使其成为研究的高度优先事项 社区。评估潜在疾病修改治疗的临床试验结果令人失望 AD/ADRD已将治疗重点转移到临床前干预(Cous-Bou等人，2017)，这需要 改进了诊断。虽然在以血液为基础的鉴定方面继续取得重大进展 对于AD/ADRD的生物标记物，一种平行的方法可以是使用眼睛成像或其他眼睛生物标记物来诊断 及早发现。这项建议目的是提供死后AD/ADRD的眼部生物标本 AD/ADRD研究眼组织资源的捐赠者以及非疾病对照捐赠者(OTR- Ad)适用于支持解决与眼睛有关的关键问题的关键调查路线 该病的发病机制。 OMB编号0925-0001/0002(批准的第03/2020版至2023年2月28日)续页格式页