The development of a therapeutic carrier

治疗载体的开发

• 批准号: 452456-2013
• 负责人: Jefferies, Wilfred
• 金额: $ 10.9万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=575539
• 关键词: development; therapeutic; carrier

Neurological diseases associated with cancers, genetic diseases, infectious diseases and aging create a significant social and economic burden. Despite advances in technologies that have spawned new drug targets and therapeutic candidates for neurological diseases, we have yet to find successful clinical therapies, due in part to disease complexity and the individual variability within the human population. However, the most serious barrier to treatment is often inefficient delivery of drugs to the disease-affected brain tissue. This is due to restrictions dictated by the existence of the blood-brain barrier (BBB). Designing efficient 'vectors' (antibodies, protein carriers, viruses, nanoparticles) to deliver therapeutics across the BBB in a controlled and non-invasive manner remains one of the key goals of drug development for brain diseases. We have demonstrated that by using a patented carrier molecule, chemotherapeutic drugs can be delivered to the brain and be effective against cancer. There also exists preliminary data in the patent that this carrier may be useful by acting as a conjugate to treat diseases of the central nervous system (CNS). The purpose of this proposal is to suggest experiments that will extend the life of the patent in order to allow this technology to be produced and therefore become useful in a therapeutic setting. This proposal outlines experiments that will provide a model the carrier protein to act as a delivery vehicle when conjugated to a therapeutic enzyme, as well as to begin to elucidate the specific interactions that take place which allow the carrier protein to transport into and across a physical cellular barrier such as the BBB.

与癌症、遗传病、传染病和老龄化相关的神经系统疾病造成了重大的社会和经济负担。尽管技术的进步催生了新的药物靶点和神经系统疾病的治疗候选人，但我们尚未找到成功的临床治疗方法，部分原因是疾病的复杂性和人群中的个体差异性。然而，最严重的治疗障碍往往是药物向受疾病影响的脑组织的低效递送。这是由于血脑屏障（BBB）的存在所决定的限制。设计有效的“载体”（抗体，蛋白质载体，病毒，纳米颗粒）以受控和非侵入性的方式将治疗药物输送到BBB仍然是脑部疾病药物开发的关键目标之一。我们已经证明，通过使用专利载体分子，化疗药物可以被递送到大脑并有效对抗癌症。在该专利中还存在这样的初步数据，即该载体可以通过作为缀合物来治疗中枢神经系统（CNS）疾病而有用。 本提案的目的是建议进行延长专利有效期的实验，以便生产这种技术，从而在治疗环境中发挥作用。 该提案概述了将提供载体蛋白与治疗酶缀合时作为递送载体的模型的实验，以及开始阐明发生的允许载体蛋白运输进入和穿过物理细胞屏障如BBB的特异性相互作用。