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Disease Modification Through Trophic Factor Delivery

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Huntington’s Disease

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1780))

Abstract

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.

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

    Mari Savolainen & Jeffrey H. Kordower

  2. NsGene, Inc., Providence, RI, USA

    Dwaine Emerich

  3. The Van Andel Research Institute, Grand Rapids, MI, USA

    Jeffrey H. Kordower

Authors
  1. Mari Savolainen
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  2. Dwaine Emerich
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  3. Jeffrey H. Kordower
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Correspondence to Jeffrey H. Kordower .

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Editors and Affiliations

  1. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Sophie V. Precious

  2. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Anne E. Rosser

  3. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Stephen B. Dunnett

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Savolainen, M., Emerich, D., Kordower, J.H. (2018). Disease Modification Through Trophic Factor Delivery. In: Precious, S., Rosser, A., Dunnett, S. (eds) Huntington’s Disease. Methods in Molecular Biology, vol 1780. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7825-0_24

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  • DOI: https://doi.org/10.1007/978-1-4939-7825-0_24

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