Improvement of HDL and atherosclerosis by a mimetic peptide (18A) complexed with niclosamide and administered orally to mice (LB532)

18A was incubated together with niclosamide and within 6h of oral administration there was significant improvement (p<0.001) in the HDL-inflammatory index (HII) in ApoE null mice. Oral L-4F alone or niclosamide alone were ineffective. Subcutaneous injection of L-4F alone but not niclosamide alone significantly improved the HII. Analysis of the L-4F-niclosamide complex by gradient gel electrophoresis or Fourier Transform Infrared Spectroscopy indicated that the self-association of L-4F was altered resulting in smaller micelles. Oral administration of L-4F and niclosamide to old apoE null mice together with pravastatin resulted in regression of lesions. In another experiment ApoE null mice 3-4 months of age were treated for 7 months with pravastatin in the drinking water and oral L-4F together with niclosamide in doses which produced maximal L-4F plasma concentrations of ~100 ng/mL. There was a significant reduction in lesion area compared to controls (p<0.001). The reduction in lesion area was not improved...