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Novel Brain-Penetrating Single Chain Antibodies Directed Against 3RTau for the Treatment of Alzheimer’s Disease and Related Dementias

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Cell Penetrating Peptides

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2383))

Abstract

Alzheimer’s disease (AD), Pick’s disease, fronto-temporal lobar degeneration, cortico-basal degeneration, and primary age related tauopathy are examples of neurodegenerative disorders with tau accumulation and jointly referred as “tauopathies.” The mechanisms through which tau leads to neurodegeneration are not fully understood but include conversion into toxic oligomers and protofibrils, cell-to-cell propagation, post-transcriptional modifications and as a mediator of cell death signals among others. Potential therapeutics includes reducing tau synthesis (e.g., anti-sense); targeting selective tau species and aggregates or blocking cell-to-cell transmission (e.g., antibodies) or by promoting clearance of tau (e.g., autophagy activators). Among them, immunotherapy is currently one of the approaches most actively explored including active, passive, and cellular. A potential problem with immunotherapy has been the trafficking of the antibodies into the CNS. In this chapter, we describe a method for the production and testing of viral vector driven, brain-penetrating, single chain antibodies that specifically recognize 3RTau. These single chain antibodies are modified by the addition of a fragment of the apoB protein to facilitate trafficking into the brain, once in the CNS these antibody fragments recognize tau with potential value for the treatment of AD and related dementias.

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Acknowledgments

Supported by NIH grants AG5131, AG018440, AG051839 to RR. HEK293 antibody production was performed by the VBCF Protein Technologies Facility (www.vbcf.ac.at).

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Authors and Affiliations

  1. Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA

    Brian Spencer, Robert A. Rissman, Cassia Overk & Eliezer Masliah

  2. Veterans Affairs San Diego Healthcare System, San Diego, CA, USA

    Robert A. Rissman

  3. Department of Pathology, University of California, San Diego, La Jolla, CA, USA

    Eliezer Masliah

  4. Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

    Eliezer Masliah

Authors
  1. Brian Spencer
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  2. Robert A. Rissman
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  3. Cassia Overk
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  4. Eliezer Masliah
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Corresponding author

Correspondence to Eliezer Masliah .

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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden

    Ülo Langel

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Spencer, B., Rissman, R.A., Overk, C., Masliah, E. (2022). Novel Brain-Penetrating Single Chain Antibodies Directed Against 3RTau for the Treatment of Alzheimer’s Disease and Related Dementias. In: Langel, Ü. (eds) Cell Penetrating Peptides. Methods in Molecular Biology, vol 2383. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1752-6_28

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  • DOI: https://doi.org/10.1007/978-1-0716-1752-6_28

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1751-9

  • Online ISBN: 978-1-0716-1752-6

  • eBook Packages: Springer Protocols

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