生物谷報(bào)道：血腦屏障一直是許多中樞系統(tǒng)疾病治療的重要難點(diǎn),，許多藥物都因?yàn)闊o法在腦內(nèi)形成有效的血藥濃度，從而使治療效果大大下降,。
剛剛在本期PNAS上,，以色列科學(xué)家Vivian I. Teichberg發(fā)現(xiàn)一種全新的方法，使透過血腦屏障變得簡(jiǎn)單,，這一方法如何大規(guī)模應(yīng)用,，將開創(chuàng)中樞神經(jīng)系統(tǒng)疾病治療的革命,，尤其是象蛋白質(zhì)類的大分子,。研究表明，在血腦屏障上有一些受體,，如果某些蛋白質(zhì)能很好地與這些受體結(jié)合,，那么就容易被輸入到中樞神經(jīng)系統(tǒng)內(nèi),。因此,，以色列科學(xué)家便尋找一種能與血腦屏障上受體結(jié)合的新的治療手段。作用使用慢病毒（lentivirus)載體系統(tǒng),，將溶酶體的一種酶---β-葡萄糖腦苷脂酶(β-glucocerebrosidase)和分泌狀態(tài)的GFP制成融合蛋白,，發(fā)現(xiàn)能成功在肝臟和腦中得到表達(dá)。進(jìn)一步,，再融合了低密度脂蛋白受體結(jié)合域到此蛋白,，進(jìn)一步促進(jìn)了蛋白透過血腦屏障進(jìn)入大腦。為此,，PNAS專門為此文發(fā)表了相關(guān)的評(píng)論,，高度評(píng)價(jià)了，這一治療方法的重要意義與價(jià)值,。
以下是目前所有的穿透血腦屏障的已有的方法的比較：
Table 1. Methods used to deliver drugs across the BBB
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Strategy Method (representative refs.) Major drawback
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Neurosurgical approach Injection within the CSF (3, 12) Limited diffusion
i.c.v. administration (13) Limited diffusion
Drug-releasing implants (5) Local delivery
Peritumoral infusion (14) Invasive
Chemical approach Liposome and nanoparticle encapsulation (15) Enter all organs
Cationization (6, 13) Enter all organs
BBB opening Intracarotid injection of hyperosmotic fluid (7) Transient opening
BBB bypass Intranasal delivery (8) Limited size of <10 kDa, limited concentration
Cell therapy Stem cell differentiation and engrafment in the CNS (16) Low yield
Gene therapy Receptor-mediated transcytosis of liposome-encapsulated RNAi and DNA (17) Repeated injection
Viral vectors (18) Invasive, limited diffusion
Protein therapy Protein overload (19) Low yield
Receptor-mediated transcytosis (9, 11) Immunoreactivity
i.c.v., intracerebroventricular.
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這是PNAS對(duì)此文的評(píng)價(jià)：
Treatment of many neuronal degenerative disorders will require delivery of a therapeutic protein to neurons or glial cells across the whole CNS. The presence of the blood–brain barrier hampers the delivery of these proteins from the blood, thus necessitating a new method for delivery. Receptors on the blood–brain barrier bind ligands to facilitate their transport to the CNS; therefore, we hypothesized that by targeting these receptors, we may be able to deliver proteins to the CNS for therapy. Here, we report the use of the lentivirus vector system to deliver the lysosomal enzyme glucocerebrosidase and a secreted form of GFP to the neurons and astrocytes in the CNS. We fused the low-density lipoprotein receptor-binding domain of the apolipoprotein B to the targeted protein. This approach proved to be feasible for delivery of the protein and could possibly be used as a general method for delivery of therapeutic proteins to the CNS.
