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HoFH Patients’ Varied Response to PCSK9 Inhibition

Arterioscler Thromb Vasc Biol; ePub 2017 Dec 28; Thedrez, et al

Residual low-density lipoprotein receptor (LDLR) expression is a major determinant of low-density lipoprotein cholesterol (LDL-C) levels and may drive their individual response to evolocumab, a recent study found. Lymphocytes were isolated from 22 HoFH patients in the TAUSSIG trial. 10 patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with our without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Researchers found:

  • All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality.
  • Lymphocytes from FH1/FH2 patients displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH2 patients.
  • Mevastatin increased, whereas rPCSK9 reduced LDLR expression.
  • Significant positive correlations were found between levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment.

Citation:

Thedrez A, Blom DJ, Ramin-Mangata S, et al. Homozygous familial hypercholesterolemia patients with identical mutations variably express the LDLR (low-density lipoprotein receptor). Implications for the efficacy of evolocumab. [Published online ahead of print December 28, 2017]. Arterioscler Thromb Vasc Biol. doi:10.1161/ATVBAHA.117.310217.

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