Novel therapies and new targets of treatment for familial hypercholesterolemia.
Patients with familial hypercholesterolemia (FH) are not always able to achieve target levels of low-density lipoprotein (LDL) cholesterol with currently available medications. A number of novel pharmaceutical approaches to LDL cholesterol-lowering have been in development. Antisense oligonucleotides are molecules that are injected subcutaneously and cause decreased release of apolipoprotein B-containing lipoproteins from the liver. Microsomal transfer protein inhibitors block the accumulation of triglyceride into apolipoprotein B precursors. Squalene synthase inhibitors partially block a late step in cholesterol biosynthesis. Proprotein convertase subtilisin kexin type 9 inhibitors can lead to increased LDL cholesterol receptor functioning and thereby decrease LDL cholesterol levels. Thyroid hormone analogues lower LDL cholesterol and other lipoproteins by a selective effect on certain thyroid hormone receptors, avoiding the adverse effects of excessive thyroid hormone levels. Several of these classes of lipid-modifying agents are currently in clinical trials. Long-term safety data will be needed before any are available to be used clinically, but some hold significant potential for improving treatment options for patients with FH.
Division of Endocrinology, Metabolism, and Lipid Research, Washington University, Campus Box 8127, 660 South Euclid, St. Louis, MO 63110, USA. agoldber@dom.wustl.edu
Anne Carol
AC
Goldberg
D001055:Apolipoproteins B / Q000235:genetics; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D013963:Thyroid Hormones / Q000737:chemistry
D001055:Apolipoproteins B; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D016376:Oligonucleotides, Antisense; D013963:Thyroid Hormones; C106092:microsomal triglyceride transfer protein; D013186:Farnesyl-Diphosphate Farnesyltransferase; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases