Neurotherapeutics

, Volume 11, Issue 4, pp 817–839

Gene Therapy for the Nervous System: Challenges and New Strategies

  • Casey A. Maguire
  • Servio H. Ramirez
  • Steven F. Merkel
  • Miguel Sena-Esteves
  • Xandra O. Breakefield
Review

DOI: 10.1007/s13311-014-0299-5

Cite this article as:
Maguire, C.A., Ramirez, S.H., Merkel, S.F. et al. Neurotherapeutics (2014) 11: 817. doi:10.1007/s13311-014-0299-5

Abstract

Current clinical treatments for central nervous system (CNS) diseases, such as Parkinson’s disease and glioblastoma do not halt disease progression and have significant treatment morbidities. Gene therapy has the potential to “permanently” correct disease by bringing in a normal gene to correct a mutant gene deficiency, knocking down mRNA of mutant alleles, and inducing cell-death in cancer cells using transgenes encoding apoptosis-inducing proteins. Promising results in clinical trials of eye disease (Leber’s congenital aumorosis) and Parkinson’s disease have shown that gene-based neurotherapeutics have great potential. The recent development of genome editing technology, such as zinc finger nucleases, TALENS, and CRISPR, has made the ultimate goal of gene correction a step closer. This review summarizes the challenges faced by gene-based neurotherapeutics and the current and recent strategies designed to overcome these barriers. We have chosen the following challenges to focus on in this review: (1) delivery vehicles (both virus and nonviral), (2) use of promoters for vector-mediated gene expression in CNS, and (3) delivery across the blood-brain barrier. The final section (4) focuses on promising pre-clinical/clinical studies of neurotherapeutics.

Keywords

Gene deliveryCentral nervous systemVirus vectorNonviral gene deliveryGene therapy

Supplementary material

13311_2014_299_MOESM1_ESM.pdf (1.2 mb)
ESM 1(PDF 1225 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2014

Authors and Affiliations

  • Casey A. Maguire
    • 1
  • Servio H. Ramirez
    • 4
  • Steven F. Merkel
    • 4
  • Miguel Sena-Esteves
    • 3
  • Xandra O. Breakefield
    • 1
    • 2
  1. 1.Department of Neurology, Massachusetts General Hospital, and Neuroscience ProgramHarvard Medical SchoolCharlestownUSA
  2. 2.Department of Radiology, Massachusetts General Hospital, Neuroscience ProgramHarvard Medical SchoolBostonUSA
  3. 3.Department of NeurologyUniversity of Massachusetts Medical SchoolWorcesterUSA
  4. 4.Pathology and Laboratory MedicineTemple University School of MedicinePhiladelphiaUSA