When I first looked at the BBB I initially thought it may only cross when bound to CCR5. After a whole lot of reading last year I figured out that a highly inflammatory state could allow leronlimab through unbound. Two very recent papers showed how it could, I had one linked in an earlier post, the second I haven't been able to track down.

But I've also surmised that leronlimab passing through the BBB may not be necessary. The macrophages, dendritic cells etc. where CCR5 is expressed are not produced in the brain. Leronlimab binding would shut down the macrophage recruitment and inflammation that damages the myelin sheath before crossing over. It would also shut down the leaky blood brain barrier that is caused by inflammation. With a cross over of unbound leronlimab there might be a slightly faster effect due to binding to already existing CCR5 receptors in the brain but it wouldn't be by much.