Scientific rationale for the development of gene therapy strategies for Parkinson's disease

Biochim Biophys Acta. 2009 Jul;1792(7):703-13. doi: 10.1016/j.bbadis.2009.02.009. Epub 2009 Feb 27.

Abstract

The ever-evolving understanding of the neuronal systems involved in Parkinson's disease together with the recent advances in recombinant viral vector technology has led to the development of several gene therapy applications that are now entering into clinical testing phase. To date, four fundamentally different approaches have been pursued utilizing recombinant adeno-associated virus and lentiviruses as vectors for delivery. These strategies aim either to restore the lost brain functions by substitution of enzymes critical for synthesis of neurotransmitters or neurotrophic factors as a means to boost the function of remaining neurons in the diseased brain. In this review we discuss the differences in mechanism of action and describe the scientific rationale behind the currently tested gene therapy approaches for Parkinson's disease in some detail and pinpoint their individual unique strengths and weaknesses.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Dihydroxyphenylalanine / genetics
  • Dihydroxyphenylalanine / metabolism
  • Dopamine / genetics
  • Dopamine / metabolism
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Parkinson Disease / genetics*
  • Parkinson Disease / therapy*
  • Subthalamic Nucleus / metabolism
  • Subthalamic Nucleus / pathology

Substances

  • Nerve Growth Factors
  • Dihydroxyphenylalanine
  • Dopamine