The development of a therapeutic carrier

与癌症、遗传疾病、传染病和衰老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神经疾病的新药物靶点和治疗候选物，但由于疾病的复杂性和人群中的个体差异，我们尚未找到成功的临床治疗方法。然而，最严重的治疗障碍往往是药物无法有效地输送到受疾病影响的脑组织。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），以可控和非侵入性的方式将治疗药物传递到血脑屏障上，仍然是脑部疾病药物开发的关键目标之一。我们已经证明，通过使用一种获得专利的载体分子，化疗药物可以被输送到大脑，并有效地对抗癌症。该专利中还存在初步数据，表明该载体可能通过作为偶联物治疗中枢神经系统（CNS）疾病而有用。本提案的目的是提出延长专利寿命的实验建议，以便使这项技术得以生产，从而在治疗环境中发挥作用。该提案概述了一些实验，这些实验将提供一个模型，使载体蛋白在与治疗酶结合时充当递送载体，并开始阐明所发生的特定相互作用，这些相互作用允许载体蛋白运输进入并穿过物理细胞屏障，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.