Gene therapy in disorders of lipoprotein metabolism.
Current pharmacologic interventions in lipid metabolism are insufficient in a subset of patients at increased risk of cardiovascular disease. In particular, several monogenetic disorders of lipid metabolism with diverse clinical complications are beyond treatment to date. Somatic gene transfer is a potential approach to treat these disorders. This review describes the efforts made thus far to develop gene therapy for 3 major classes of dyslipidemia: Increased levels of low-density lipoprotein cholesterol, reduced levels of high-density lipoprotein cholesterol and increased plasma triglyceride levels. For many of the genetic causes underlying these conditions, proof-of-principle studies have been performed and in combination with improved vectors some of these strategies may be feasible for clinical use in the future.
Vaessen
Stefan F C
SF
Department of Vascular Medicine, Academic Medical Center, 1105 AZ, Amsterdam, the Netherlands.
Twisk
Jaap
J
Kastelein
John J P
JJ
Kuivenhoven
Jan Albert
JA
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006224:Cricetinae; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000145:classification* / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D011817:Rabbits; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides