The development of a therapeutic carrier

与癌症、遗传病、传染病和老龄化相关的神经系统疾病造成巨大的社会和经济负担。尽管技术进步催生了神经疾病的新药物靶点和治疗候选药物，但我们尚未找到成功的临床疗法，部分原因是疾病的复杂性和人类群体中的个体差异。然而，最严重的治疗障碍往往是向受疾病影响的脑组织输送药物的效率低下。这是由于血脑屏障(BBB)的存在所造成的限制。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在血脑屏障内传递治疗药物，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，化疗药物可以被输送到大脑，并对癌症有效。专利中也有初步数据表明，该载体可作为治疗中枢神经系统(CNS)疾病的结合物而有用。这项提议的目的是提出延长专利寿命的实验，以便使这项技术能够被生产出来，从而在治疗环境中变得有用。这项提案概述了一些实验，这些实验将提供一个模型，即载体蛋白在与治疗性酶结合时充当传递载体，并开始阐明发生的特定相互作用，使载体蛋白能够进入和穿过物理细胞屏障，如血脑屏障。

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.