bms201038 and Coronary-Disease

Homozygous hypercholesterolemia is an extremely rare genetic disorder caused by mutations in the LDL receptor gene or occasionally by mutations in other genes like proprotein convertase subtilisin / kexin 9 (PCSK9). Gold standard of homozygous hypercholesterolemia therapy is apheresis, accompanied by high-dose statin and ezetimibe therapy. The cholesterol-lowering effect can be supported by new agents like inhibitors of microsomal triglyceride transfer protein (lomitapide), or by enhancing LDL catabolism through inhibition of the PCSK9 activity. We present the case of a young woman with homozygous hyperlipidemia due to a mutation c.1200 C> A(p.Tyr400*) in the LDLR gene that introduces a stop-codon at amino acid position 400. This truncated LDLR cannot mediate a membrane-bound uptake of LDL cholesterol. A combined therapy including simvastatin, ezetimibe and apheresis did not lead to satisfactory LDL levels. By adding lomitapide, a dramatic receptor-independent reduction of LDL was achieved.

Topics: Adult; Anticholesteremic Agents; Benzimidazoles; Blood Component Removal; Codon, Terminator; Combined Modality Therapy; Coronary Disease; DNA Mutational Analysis; Ezetimibe; Female; Homozygote; Humans; Hyperlipoproteinemia Type II; Myocardial Revascularization; Receptors, LDL; Simvastatin

Hypercholesterolemia affects over 34 million adults in the United States and is a major cause of coronary heart disease (CHD). Conventional therapies, such as statins, have demonstrated their ability to improve clinical end points and decrease morbidity and mortality in patients with CHD. Lomitapide (Juxtapid(®)), mipomersen (Kynamro(®)), and icosapent (Vascepa(®)) are 3 novel agents approved by the US Food and Drug Administration in the past 2 years, which offer new lipid-lowering treatment options with unique pharmacology.

Topics: Adult; Anticholesteremic Agents; Benzimidazoles; Coronary Disease; Drug Approval; Eicosapentaenoic Acid; Humans; Hypercholesterolemia; Oligonucleotides; United States; United States Food and Drug Administration