It is important to note that although the study shows that I-S1 crosses the BBB in mice, this may not be the case in humans. For that reason, we used in vitro models of the human BBB, which can be useful in studying mechanisms of BBB permeability.
In this model, we did not observe significant differences in permeability for I-S1 compared to T-Alb. The apparent absence of I-S1 transport across the BBB in this in vitro model could be due to technical issues, such as blockers of I-S1 binding in the buffers. It could also mean that the iBECs did not express the cell-membrane glycoproteins necessary for I-S1 transport, or that I-S1 is not able to cross the human BBB.
https://www.nature.com/articles/s41593-020-00771-8