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Gene Therapy in the Nervous System: Failures and Successes

  • Jayanth S. Chandran
  • Joseph M. Scarrott
  • Pamela J. Shaw
  • Mimoun AzzouzEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1007)

Abstract

Genetic disorders, caused by deleterious changes in the DNA sequence away from the normal genomic sequence, affect millions of people worldwide. Gene therapy as a treatment option for patients is an attractive proposition due to its conceptual simplicity. In principle, gene therapy involves correcting the genetic disorder by either restoring a normal functioning copy of a gene or reducing the toxicity arising from a mutated gene. In this way specific genetic function can be restored without altering the expression of other genes and the proteins they encode. The reality however is much more complex, and as a result the vector systems used to deliver gene therapies have by necessity continued to evolve and improve over time with respect to safety profile, efficiency, and long-term expression. In this chapter we examine the current approaches to gene therapy, assess the different gene delivery systems utilized, and highlight the failures and successes of relevant clinical trials. We do not intend for this chapter to be a comprehensive and exhaustive assessment of all clinical trials that have been conducted in the CNS, but instead will focus on specific diseases that have seen successes and failures with different gene therapy vehicles to gauge how preclinical models have informed the design of clinical trials.

Keywords

Adeno-associated virus Gene therapy CNS Neurodegenerative disease Antisense oligonucleotides 

Notes

Acknowledgements

MA and JSC are supported by an ERC Advanced Investigator Award. JMS is supported by University of Sheffield studentship. PJS is supported as an NIHR Senior Investigator.

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Jayanth S. Chandran
    • 1
  • Joseph M. Scarrott
    • 1
  • Pamela J. Shaw
    • 1
  • Mimoun Azzouz
    • 1
    Email author
  1. 1.Sheffield Institute for Translational NeuroscienceUniversity of SheffieldSheffieldUK

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