The application of gene therapy in lipid disorders: where are we now?

Abstract

Lipid disorders or dyslipidemias result from perturbations within the biochemical pathways that regulate lipid metabolism. The dramatically altered lipid profiles that sometimes result from defects in these pathways can greatly enhance the risk of cardiovascular disease or other complications, with an attendant negative impact on morbidity and mortality. Patients with rare monogenic forms of dyslipidemia often live highly restrictive lifestyles, and options among existing pharmaceutical treatments are limited. Gene therapy provides a potential treatment option for monogenic dyslipidemias and perhaps even a long-term stable cure. In this article, we review the gene therapies applied to two types of monogenic dyslipidemias: homozygous familial hypercholesterolemia and familial LPL deficiency. We discuss the limitations of this approach, consider some future directions of gene therapy for monogenic dyslipidemias and possibilities for polygenic dyslipidemias.

Key Words:

• alipogene tiparvovec
• dyslipidemia
• familial hypercholesterolemia
• gene therapy
• LPL deficiency
• monogenic disease