Recent Developments in Gene Therapy for Homozygous Familial Hypercholesterolemia
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  • 作者：Ezim Ajufo ; Marina Cuchel
  • 关键词：Gene therapy ; Homozygous familial hypercholesterolemia ; LDL receptor ; Adeno ; associated virus (AAV) ; Adenovirus ; iPSC
  • 刊名：Current Atherosclerosis Reports
  • 出版年：2016
  • 出版时间：May 2016
  • 年：2016
  • 卷：18
  • 期：5
  • 全文大小：351 KB
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  • 作者单位：Ezim Ajufo (1)
    Marina Cuchel (1)

    1. Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • 刊物主题：Angiology; Cardiology;
  • 出版者：Springer US
  • ISSN：1534-6242
    • 文摘
    Homozygous familial hypercholesterolemia (HoFH) is a life-threatening Mendelian disorder with a mean life expectancy of 33 years despite maximally tolerated standard lipid-lowering therapies. This disease is an ideal candidate for gene therapy, and in the last few years, a number of exciting developments have brought this approach closer to the clinic than ever before. In this review, we discuss in detail the most advanced of these developments, a recombinant adeno-associated virus (AAV) vector carrying a low-density lipoprotein receptor (LDLR) transgene which has recently entered phase 1/2a testing. We also review ongoing development of approaches to enhance transgene expression, improve the efficiency of hepatocyte transduction, and minimize the AAV capsid-specific adaptive immune response. We include a summary of key gene therapy approaches for HoFH in pre-clinical development, including RNA silencing of the gene encoding HMG-CoA reductase (HMGCR) and induced pluripotent stem cell transplant therapy.

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