Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia.
To investigate the impact of mipomersen, an apolipoprotein B-100 (apoB) synthesis inhibitor, on intra-hepatic triglyceride content (IHTG content), we conducted a randomized, double-blind, placebo-controlled study in 21 patients with familial hypercholesterolemia (FH). Subjects received a weekly subcutaneous dose of 200 mg mipomersen or placebo for 13 weeks while continuing conventional lipid lowering therapy. The primary endpoint was change in IHTG content from week 0 to week 15 as measured by localized proton magnetic resonance spectroscopy (1H-MRS). Thirteen weeks of mipomersen administration reduced LDL-cholesterol by 22.0 (17.8) % and apoB by 19.9 (17.4) % (both P < 0.01). One of 10 patients (10%) in the mipomersen-treated group developed mild hepatic steatosis at week 15, which was reversible following mipomersen discontinuation. For the group, there was a trend toward an increase in IHTG content [placebo; baseline: 1.2% and week 15: 1.1%; change -0.1 (0.9). Mipomersen; baseline: 1.2% and week 15: 2.1%; change 0.8 (1.7) (P = 0.0513)]. Mipomersen administration for 13 weeks to subjects with FH is associated with a trend toward an increase in IHTG content. Future studies evaluating the effects of long-term use of mipomersen reaching more profound reductions in apoB are required prior to broader use of this compound.
Visser
Maartje E
ME
Department of Vascular Medicine, Academic Medical Center Amsterdam, The Netherlands.
Akdim
Fatima
F
Tribble
Diane L
DL
Nederveen
Aart J
AJ
Kwoh
T Jesse
TJ
Kastelein
John J P
JJ
Trip
Mieke D
MD
Stroes
Erik S G
ES
D000293:Adolescent; D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000096:biosynthesis*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000009:adverse effects / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism*; D055815:Young Adult
D001055:Apolipoproteins B; D009841:Oligonucleotides; D014280:Triglycerides; C524142:mipomersen