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MS quite often has a genetic basis but the triggers seem to be mostly environmental. Viruses, bacteria pollution or anything else that can dysregulate immune response and increase immune response leading to autoimmunity directed to the nerve system's myelin sheath.

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The initial autoimmunity is driven by Th1 and Th17 inflammatory T-cells. The increase in Th1 and Th17 cells increase CCR5 and other immune receptors and in return CCR5 and other receptors increases Th1 and Th17 cells in a feedback loop. Th1 and Th17 cells increase CCL2, CCL3, CCL4, CCL5, and CCL7 ligands that bind to CCR5. Which in turn increases inflammatory cytokines like IFNy, IL-1b, IL-17, IL-21, GM-CSF, TNF-a, NF-kb, MAPk, PI3k and others.

CCR5 and those inflammatory cytokines increase and activate the microglia and astrocytes that attack the myelin sheath. The degraded myelin exposes the nerve fibers to further attacks and can kill them.

Where leronlimab comes in is that the CCR5 blockade decreases Th1 and Th17 expression. It eliminates the binding of CCL2, CCL3, CCL4, CCL5, and CCL7 and other ligands to CCR5. It downregulates the cytokines that are listed and other inflammatory cytokines. It downregulates a few of the complementary receptors such as CX3CL1, CXCL8 and CXCR4. It leaves the other receptors open to accomplish normal immune functions while controlling the overactive immune function.

Why CCR5 rather than other receptors? CCR5 blockade binds quite an array of ligands. Most importantly it has the highest binding ability for CCL5 and CCL5 is probably the most prolific ligand for chemotaxis. With less chemotaxis you have less cytokines directed to the problem sites.

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