Blockade of chemokine signaling in patients with multiple sclerosis

The CC chemokine receptor 1 (CCR1), expressed on macrophages and T cells, and its ligands, CCL3 and CCL5, are likely to play a role in MS pathology. In MS plaques, numerous CCR1-positive infiltrating macrophages and microglial cells, especially associated with CCL3, were found. 1 CCR1 has been associated with newly infiltrating monocytes in MS lesions.(2) The degree of leukocyte infiltration into the CNS during experimental autoimmune encephalomyelitis (EAE) was reduced on treatment with a specific CCR1 antagonist.(3) CCR1-deficient mice showed an attenuated EAE course.(4) A small-molecule antagonist of CCR1, BX 471, was able to reduce the severity of EAE(5) and delay heart transplant rejection. 6 Here, we investigated the safety, tolerability, and effects of BX 471, which was developed with a potential for oral therapy.