Disease Modification Through Trophic Factor Delivery

  • Mari Savolainen
  • Dwaine Emerich
  • Jeffrey H. KordowerEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1780)


Huntington’s disease (HD) is characterized by a significant loss of striatal neurons that project to the globus pallidus and substantia nigra, together with loss of cortical projection neurons in varying regions. Mutant huntingtin is suggested to drive the pathogenesis partially by downregulating corticostriatal brain-derived neurotrophic factor (BDNF) levels and signaling. Neurotrophic factors are endogenous peptides that promote the survival and maintenance of neurons. BDNF and other neurotrophic factors have shown neuroprotective benefits in various animal models of neurodegeneration, and are interesting candidates to protect the cell populations that are destined to die in HD. In an attempt to enhance the delivery of neurotrophic factors, several methods have been established to deliver long-term neurotrophic factor gene therapy to human target tissues. This chapter discusses two alternative approaches that have been shown to have potential to deliver neurotrophic factors as a neuroprotective gene therapy for HD. The methods are (1) ex vivo approach where encapsulated cells engineered to express neurotrophic factor are inserted into brain parenchyma or ventricle, and (2) in vivo viral vector therapy, in which viral vector is injected into desired brain area to express gene of interest in the host cells.


Neurotrophic factors Glial-derived neurotrophic factor, GDNF Ciliary neurotrophic factor, CDNF Neurturin Gene therapy Adeno-associated viral vector, AAV Encapsulated cells 



Mari Savolainen is funded by The Finnish Cultural Foundation, The Finnish Parkinsons Foundation, and The Maud Kuistila Memorial Foundation.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mari Savolainen
    • 1
  • Dwaine Emerich
    • 2
  • Jeffrey H. Kordower
    • 1
    • 3
    Email author
  1. 1.Department of Neurological SciencesRush University Medical CenterChicagoUSA
  2. 2.NsGene, Inc.ProvidenceUSA
  3. 3.The Van Andel Research InstituteGrand RapidsUSA

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