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：
10677750
负责人：
Michele M Mulholland
金额：
$ 18.98万
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/10677750
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 Neurologic Examination 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 Therapeutic Training Translational Research Treatment-Related Cancer age related age related neurodegeneration aging brain cancer therapy career chemobrain chemotherapy cognitive ability cognitive change 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 neural neuropathology nonhuman primate novel preclinical study prevent success tau Proteins tau-1 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.

项目摘要化学疗法是对癌症的极有效疗法。但是，与化学疗法的好处一起有许多不良后果，包括与化学疗法相关的认知障碍（CRCI）和加速衰老。尽管对生活质量产生了影响，但这些领域还是相对了解的目前尚无FDA批准的治疗。解决这个问题的复杂动物模型将是非常有价值，无论是我们对长期后果的理解和发展的理解潜在治疗。目前，CRCI和与化疗相关的加速衰老在啮齿动物中是研究的，但是非人类私人模型将显着提高解决此问题仍未进行研究的研究的有效性现象。在这项拟议的研究中，我们旨在建立CRCI和加速衰老的狒狒模型。我们将进一步定义狒狒样品中的健康衰老，然后研究化学疗法是否诱导认知像人类一样衰落和加速狒狒的大脑衰老，并测试一种干预措施在小鼠中有效。我们将从狒狒那里收集大脑成像，认知和衰老的分子生物标志物数据在仅用顺铂或顺铂治疗之前，然后是HDAC6抑制剂。然后我们将进一步收集治疗后的大脑，认知和衰老数据，以检查与化学疗法方案相关的变化和 HDAC6抑制剂是否会逆转认知能力下降和神经变性。这些数据将用于提出进一步的研究和技术，以减轻化学疗法的这些后果人类。