Anti-AVM antibody was used as a negative control. brain for a short time. To overcome this problem, we developed a different approach which slows down the export of therapeutic antibodies from the brain by binding them to a brain-specific antigen. Here we report a new technology, named AccumuBrain, that achieves Oleuropein both high antibody concentration in the brain and a long half-life in blood by binding to Oleuropein myelin oligodendrocyte glycoprotein (MOG), which is specifically expressed in oligodendrocytes. We report that, using our technology, anti-MOG antibody levels in the brains of mice (Mus musculus) and rats (Rattus norvegicus) were increased several tens of times for a period of one month. The mechanism of this technology is different from that of RMT technologies like TfR and IL20RB antibody would constitute a breakthrough for central nervous system disease therapeutics. == Introduction == There are many protein therapeutics, including antibodies and enzymes, undergoing clinical trials for central nerve system (CNS) diseases. It is well known that Oleuropein delivery of protein therapeutics into the brain remains challenging due to the difficulty of Oleuropein crossing the blood-brain barrier (BBB). This is illustrated by the fact that the concentration ratio of IgG in CNS relative to plasma has been reported to be in the range of 1 1:500 [15]. Therapeutic enzymes are effective against, and have been approved for, lysosomal storage diseases such as Fabry disease and Gaucher disease, but they are not effective against central nervous system conditions because their molecular weight is too high to allow for passage across the BBB [6,7]. To increase the concentration of therapeutic proteins in the brain, direct intrathecal and intracerebral injection has been tested, but the procedure is highly invasive [8]. Furthermore, it is reported that IgG are rapidly discharged from the brain into circulating blood by neonatal Fc receptor (FcRn) [9,10]. To overcome these problems, extensive research has been undertaken into technologies for delivering drugs into the brain. Most popular technologies use a receptor-mediated transcytosis (RMT)-based mechanism, and there are many reports of antibodies which bind to the transferrin receptor (TfR), which is expressed in endothelial cells, including those of the BBB, and allows for transport across the BBB by RMT [11,12]. Additionally, other receptors, such as the insulin receptor, are also reportedly transported across the BBB by means of RMT [13]. For clinical use, anti-TfR antibody or anti-insulin receptor antibody are fused with therapeutic antibodies or enzymes. One example is the anti-BACE1 anti-TfR bispecific antibody, which is transported across the BBB by RMT of TfR and has been found to be present in the brain at levels four times higher than that in control mice [14]. Other examples include anti-insulin receptor antibodies fused with glial cell-derived neurotrophic factor (GDNF) or iduronidase (IDUA). Anti-insulin receptor antibody GDNF fusion protein concentration is reported to display a 10-fold increase in the brains of Rhesus monkeys (Macaca mulatta) [13]. Anti-TfR antibody and anti-insulin receptor antibody are clearly useful in applications requiring transport of large molecules across the BBB, and for increasing antibody concentrations in the brain. However, TfR and the insulin receptor are expressed not only in the vascular endothelial cells of the brain, but also in those of other organs, as well as in other cells types in, for instance, the liver [15]. These technologies therefore deliver drugs to tissues other than the brain. Consequently, anti-TfR antibody has a short half-life in the blood [11]. For this reason, the effectiveness of therapeutic antibodies that natively have a long half-life in the blood is significantly reduced if they bind to TfR. In order to increase the half-life of anti-TfR antibodies in the blood, some studies have attempted to reduce their binding strength or valence [14,16]. However, there remains a trade-off relationship for anti-TfR antibodies between high delivery ability into the brain and long half-life in the blood. Therefore, we adopted a different approach that did not make use of the RMT concept. RMT enhances antibody transport across Oleuropein the BBB, but antibodies are also distributed in the body wherever antigens like TfR are expressed. We focused on slowing down antibody export from the brain, by binding the antibodies to a brain-specific antigen. This antigen, myelin oligodendrocyte glycoprotein (MOG), which belongs to the immunoglobulin superfamily, is specifically expressed in oligodendrocytes. Oligodendrocytes exist only.