Baboon model of chemotherapy-related cognitive impairment and accelerated aging

化疗相关认知障碍和加速衰老的狒狒模型

基本信息

批准号：
10505742
负责人：
Michele M Mulholland
金额：
$ 19.14万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
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：
2022-08-15 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10505742
关键词：
Acceleration Address Adult Aftercare Age Age of Onset Aging Alzheimer&apos s Disease Animal Model Antineoplastic Agents Area Behavior Biological Markers Biology of Aging Blood specimen Brain Brain imaging Cancer Model Characteristics Chemotherapy-Oncologic Procedure Cisplatin Clinical Trials Cognition Cognitive Cognitive aging Complex Data Dementia Development Disease Effectiveness of Interventions Elderly FDA approved Foundations Future Genetic Goals HDAC6 gene Human Impaired cognition Intervention K-Series Research Career Programs Link Malignant Neoplasms Microtubules Modeling Molecular Mus Nerve Degeneration Neuroanatomy Neurobehavioral Manifestations Neurologic Papio Papio anubis Pathology Patients Pharmaceutical Preparations Population Primates Quality of life Research Research Personnel Risk Factors Rodent Rodent Model Sampling Structure Synapses System Techniques Testing Training Translational Research Treatment-Related Cancer age related age related neurodegeneration aging brain base cancer therapy career chemobrain chemotherapy cognitive ability cognitive change cognitive development cognitive function cognitive performance cognitive testing density design drug development early onset effective therapy effectiveness evaluation experience frontal lobe gray matter healthy aging improved in vivo inhibitor innovation molecular marker multimodality nervous system disorder neuropathology nonhuman primate novel preclinical study prevent relating to nervous system success tau Proteins tau phosphorylation therapy development white matter

项目摘要

Project Summary Chemotherapy is an extremely effective treatment for cancer; however, along with chemotherapy’s benefits there are many undesirable consequences including chemotherapy-related cognitive impairments (CRCI) and accelerated aging. Despite impacts on quality of life, these areas are relatively understudied and there are currently no FDA approved treatments available. A sophisticated animal model to address this problem will be extremely valuable, both to our understanding of the long-term consequences and to the development of potential treatments. Currently, CRCI and chemotherapy-related accelerated aging is studied in rodents, but a nonhuman primate model will significantly enhance the validity of studies addressing this still under-researched phenomenon. In this proposed study, we aim to establish a baboon model of CRCI and accelerated aging. We will further define healthy aging in a baboon sample, then investigate whether chemotherapy induces cognitive decline and accelerates brain aging in baboons as it does in humans and test an intervention which has been effective in mice. We will collect brain imaging, cognitive, and aging molecular biomarker data from baboons prior to treatment with cisplatin only or cisplatin followed by an HDAC6 inhibitor. We will then collect further brain, cognitive, and aging data post-treatment to examine changes related to the chemotherapy regimen and whether the HDAC6 inhibitor reverses cognitive declines and neurodegeneration. These data will be used to propose further studies as well as techniques to potentially mitigate these consequences of chemotherapy in humans.

项目概要化疗是一种极其有效的癌症治疗方法，但化疗也有其益处。有许多不良后果，包括化疗相关的认知障碍（CRCI）和尽管加速老龄化对生活质量有影响，但这些领域的研究相对不足，而且存在一些问题。目前还没有 FDA 批准的治疗方法可以解决这个问题。对于我们了解长期后果和发展目前，CRCI 和化疗相关的加速衰老正在啮齿类动物中进行研究，但尚无定论。非人类灵长类动物模型将显着提高解决这一仍待研究的问题的研究的有效性在这项拟议的研究中，我们的目标是建立 CRCI 和加速衰老的狒狒模型。将进一步定义狒狒样本中的健康衰老，然后研究化疗是否会诱导认知能力与人类一样，狒狒的大脑老化速度下降并加速，并测试了一项已被证实的干预措施我们将从狒狒身上收集大脑成像、认知和衰老分子生物标志物数据。在仅用顺铂治疗之前或在顺铂随后使用 HDAC6 抑制剂治疗之前，我们将进一步收集。治疗后的大脑、认知和衰老数据，以检查与化疗方案相关的变化 HDAC6 抑制剂是否可以逆转认知能力下降和神经退行性变。提出进一步的研究以及技术来潜在地减轻化疗的这些后果人类。