Nathalie Van Den Berge

Passive Immunization in Alpha-Synuclein Preclinical Animal Models

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

DOI

  • Jonas Folke, University of Duisburg-Essen, University of Copenhagen
  • ,
  • Nelson Ferreira
  • ,
  • Tomasz Brudek, Research Laboratory for Stereology and Neuroscience, University of Copenhagen, Copenhagen Centre for Translational Research
  • ,
  • Per Borghammer
  • Nathalie Van Den Berge

Alpha-synucleinopathies include Parkinson’s disease, dementia with Lewy bodies, pure autonomic failure and multiple system atrophy. These are all progressive neurodegenerative diseases that are characterized by pathological misfolding and accumulation of the protein alpha-synuclein (αsyn) in neurons, axons or glial cells in the brain, but also in other organs. The abnormal accumulation and propagation of pathogenic αsyn across the autonomic connectome is associated with progressive loss of neurons in the brain and peripheral organs, resulting in motor and nonmotor symptoms. To date, no cure is available for synucleinopathies, and therapy is limited to symptomatic treatment of motor and non-motor symptoms upon diagnosis. Recent advances using passive immunization that target different αsyn structures show great potential to block disease progression in rodent studies of synucleinopathies. However, passive immunotherapy in clinical trials has been proven safe but less effective than in preclinical conditions. Here we review current achievements of passive immunotherapy in animal models of synucleinopathies. Furthermore, we propose new research strategies to increase translational outcome in patient studies, (1) by using antibodies against immature conformations of pathogenic αsyn (monomers, post-translationally modified monomers, oligomers and protofibrils) and (2) by focusing treatment on body-first synucleinopathies where damage in the brain is still limited and effective immunization could potentially stop disease progression by blocking the spread of pathogenic αsyn from peripheral organs to the brain.

Original languageEnglish
Article number168
JournalBiomolecules
Volume12
Issue2
DOIs
Publication statusPublished - Feb 2022

Bibliographical note

Funding Information:
Funding: Nathalie Van Den Berge is funded by the Lundbeck Foundation (R322-2019-2544), Jascha Foundation, Danish Parkinson’s ?ssociation and Bjarne Saxhofs fond. Jonas Folke is funded by the Danish Independent Research Fund and Danish Parkinson’s ?ssociation.

Funding Information:
Nathalie Van Den Berge is funded by the Lundbeck Foundation (R322-2019-2544), Jascha Foundation, Danish Parkinson?s Association and Bjarne Saxhofs fond. Jonas Folke is funded by the Danish Independent Research Fund and Danish Parkinson?s Association.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

    Research areas

  • Alpha-synuclein, Disease stratification, Passive immunization

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