👤 Koutaro Yokote

Recently, we reported that a pemafibrate extended-release (XR) formulation lowered low-density lipoprotein cholesterol (LDL-C) and cholesterol synthesis and absorption markers in a phase 2 clinical pharmacology study. Here we describe our post-hoc analysis of that study, discuss the mechanism by which pemafibrate lowers LDL-C, and suggest which patients may respond favorably to pemafibrate treatment. In the phase 2 study, patients with hypertriglyceridemia received treatment with pemafibrate immediate-release (IR) 0.2 mg/day or XR 0.4 mg/day or 0.8 mg/day. This post-hoc subgroup analysis examined the percentage change in LDL-C, apolipoprotein B (ApoB), non-HDL-C, and cholesterol synthesis and absorption markers, in subgroups by baseline LDL-C, and then determined the correlation between the percentage change in LDL-C and the percentage change in cholesterol synthesis and absorption markers. Our analysis included 60 patients who received two of three formulations of the drug. A total of 78.3% (47/60) were male, 16.7% (10/60) had type 2 diabetes mellitus, and 10% (6/60) received concomitant statins. The percentage of LDL-C lowering was greater in the population with high baseline LDL-C, and similar trends were noted for the ApoB, non-HDL-C, and cholesterol synthesis and absorption markers. The percentage change in LDL-C was positively correlated with the percentage change in lathosterol, β-sitosterol, and campesterol. In patients with hypertriglyceridemia, results suggested that pemafibrate lowered LDL-C by inhibiting cholesterol synthesis in the liver and cholesterol absorption from the intestinal tract. This lowering effect was greater in populations with higher baseline LDL-C. Show less

Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and early diagnosis of TIA is extremely important for the prevention of CI. We set out to identify novel antibody biomarkers for TIA and CI, and detected matrix metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5 (CBX5) as candidate antigens using serological identification of antigens by recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the presence of serum antibodies against the antigens. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that serum antibody levels were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors ( Show less