大脑可以说是人体最神秘的器官之一。不仅人类的思想由此产生，而且这一器官还享受着高标准的保护措施——血脑屏障。血脑屏障有助于保护大脑不受大部分有毒物质和病原体的侵害，可谓是功勋累累。然而，当脑部出现疾病问题，需要治疗时，血脑屏障又成为令所有医药开发者头痛的问题。
不过，大脑并不是人体中的一座孤岛。它与其他部位通过血脑屏障处细胞的转胞吞作用时刻进行着密切的物质交流。最近，美国生物技术公司基因泰克（Genentech）的研究人员可能找到了克服这一天然屏障的法宝，这一研究成果已经被发表在著名期刊Neuron上。
早期研究显示，当特异性抗体与转铁蛋白受体相结合时，该受体会出现短暂毒性并影响红细胞进而导致暂时性贫血。受此发现启发，基因泰克研究人员首先在血脑屏障处确定了两种蛋白——脂蛋白受体相关蛋白1和胰岛素受体并合成相关抗体并检测其是否能够作为克服血脑屏障的突破口。然而随后实验表明，这两种蛋白在血脑屏障处的表达水平过低。
不过研究人员并未气馁，他们利用蛋白组学的方法确定了三种在血脑屏障处高表达的受体蛋白，并通过抗体实验确定了其中一种名为CD98hc辅助穿透血脑屏障的效率最高。随后，研究人员合成了一种能够同时靶向CD98hc和β-分泌酶的双特异性抗体，后者与阿尔兹海默症有密切联系。结果发现通过这一方法不但可以将抗体输送至脑部，同时还不会改变CD98hc的表达和活性。研究人员还表示，今后可以将各种相关药物与抗体偶联起来以跨越血脑屏障达到治疗目的。
当然，目前这一研究仍然处于早期阶段。要想把血脑屏障这一天堑变成通途，还需要科学家们持续不断的努力。但至少我们已经看到了希望。
信源：New avenues into brain could deliver therapeutics
推荐的英文文献：
Discovery of Novel Blood-Brain Barrier Targets to Enhance Brain Uptake of Therapeutic Antibodiesa
DOI: http://dx.doi.org/10.1016/j.neuron.2015.11.024
The blood-brain barrier (BBB) poses a major challenge for developing effective antibody therapies for neurological diseases. Using transcriptomic and proteomic profiling, we searched for proteins in mouse brain endothelial cells (BECs) that could potentially be exploited to transport antibodies across the BBB. Due to their limited protein abundance, neither antibodies against literature-identified targets nor BBB-enriched proteins identified by microarray facilitated significant antibody brain uptake. Using proteomic analysis of isolated mouse BECs, we identified multiple highly expressed proteins, including basigin, Glut1, and CD98hc. Antibodies to each of these targets were significantly enriched in the brain after administration in vivo. In particular, antibodies against CD98hc showed robust accumulation in brain after systemic dosing, and a significant pharmacodynamic response as measured by brain Aβ reduction. The discovery of CD98hc as a robust receptor-mediated transcytosis pathway for antibody delivery to the brain expands the current approaches available for enhancing brain uptake of therapeutic antibodies.