Development and clinical assessment of novel biomarker drugs targeting SSAT1 for detection and therapeutic monitoring of glioblastoma

用于胶质母细胞瘤检测和治疗监测的新型靶向 SSAT1 生物标志物药物的开发和临床评估

• 批准号: 538823-2019
• 负责人: Miller, Donald
• 金额: $ 18.17万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=697782
• 关键词: Development; clinical; assessment; novel; biomarker

Glioblastoma multiforme (GBM) is the most common brain tumor in adults and is a death sentence for patients. The strikingly poor survival for patients with GBM (average survival 14- 16 months following diagnosis) is due in part to limited early detection methods and an absence of effective therapeutic options. The studies proposed would establish important evidence for the use of Health Canada approved drugs such as amantadine and rimantadine as a safe, effective and affordable way to monitor GBM. The method is based on the overproduction of a key enzyme in GBM cells called spermine/ spermadine n-acetyl transferase (SSAT1). The increased SSAT1 expression in GBM results in increased metabolism of the drug which is detected in the blood or urine of patients with GBM. Studies will provide evidence for the effectiveness of the drug amantadine, in detecting GBM in both cell culture and accepted rodent brain tumor models. Other drugs with similar chemical structure to amantadine will be examined in the cell culture and animal models to optimize the drug biomarker for brain penetration and tumor cell activity. The studies will conclude with an initial assessment of the selected drug biomarker in patients with GBM to determine feasibility for clinical brain tumor applications. These bench to bedside studies will be utilized by our industrial partner, BioMark Diagnostics, to help improve identification and care for patients with GB

多形性胶质母细胞瘤（GBM）是成人中最常见的脑肿瘤，对患者来说是死刑。GBM患者的生存率非常低（诊断后平均生存14- 16个月），部分原因是早期检测方法有限，缺乏有效的治疗选择。拟议的研究将建立重要的 使用加拿大卫生部批准的药物（如金刚烷胺和金刚乙胺）作为监测GBM的安全、有效和负担得起的方法的证据。该方法基于GBM细胞中一种称为精胺/精胺N-乙酰转移酶（SSAT 1）的关键酶的过度生产。GBM中SSAT 1表达的增加导致GBM代谢的增加。 在GBM患者的血液或尿液中检测到的药物。研究将为金刚烷胺药物在细胞培养和公认的啮齿动物脑肿瘤模型中检测GBM的有效性提供证据。与金刚烷胺化学结构相似的其他药物将在细胞培养和动物模型中进行检查，以优化药物 脑渗透和肿瘤细胞活性的生物标志物。这些研究将在GBM患者中对选定的药物生物标志物进行初步评估，以确定临床脑肿瘤应用的可行性。我们的工业合作伙伴BioMark Diagnostics将利用这些从实验室到床边的研究，帮助改善患者的识别和护理 与GB