Table 2:

Targeting the chemokines in human fibrosis-associated conditions

Condition	Anti-chemokine approach	Findings	Reference
Lupus nephritis	Inhibition of CCL2 (and other CC chemokines) through administration of bindarit	In a randomized double-blind clinical trial, treatment of acute lupus nephritis patients with bindarit reduced proteinuria. Fibrosis-related endpoints were not assessed.	[105]
Diabetic nephropathy (albuminuria)	Treatment with a CCR2 inhibitor (CCX140-B)	In a randomized double-blind placebo-controlled trial, CCR2 inhibition reduced proteinuria in patients with type 2 diabetes. Fibrosis-related endpoints were not assessed.	[86]
Diabetic nephropathy (albuminuria)	Treatment with emapticap pegol (NOX-E36), an L-aptamer that binds and inhibits CCL2.	In a phase IIa study, CCL2 inhibition was safe and well-tolerated and reduced the albumin to creatinine ratio. Fibrosis-related endpoints were not assessed.	[87]
Idiopathic pulmonary fibrosis (IPF)	Monoclonal anti-CCL2 neutralizing antibody (carlumab)	In a phase 2 trial, CCL2 inhibition did not affect forced vital capacity and the change in diffusing capacity in IPF patients.	[106]
HIV-infected patients	Oral CCR2/CCR5 antagonist (cenicriviroc)	In HIV-infected patients on stable antiretroviral therapy, cenicriviroc reduced plasma biomarkers of fibrosis	[88]
Hepatic fibrosis associated with HIV infection	Oral CCR2/CCR5 antagonist (cenicriviroc)	Cenicriviroc decreased the enhanced liver fibrosis index in HIV-infected patients.	[107]
Non-alcoholic steatohepatitis accompanied by liver fibrosis	Oral CCR2/CCR5 antagonist (cenicriviroc)	In a phase 2b randomized-controlled trial (CENTAUR) cenicriviroc was well tolerated and reduced fibrosis progression.	[89],[90]