Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut
Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut
Alpha synuclein has a key role in the pathogenesis of Parkinson's disease (PD), Dementia with Lewy Bodies (LBD) and Multiple System Atrophy (MSA). Immunotherapies aiming at neutralising toxic αSyn species are being investigated in the clinic as potential disease modifying therapies for PD and other synucleinopathies. In this study, the effects of active immunisation against αSyn with the UB-312 vaccine were investigated in the Thy1SNCA/15 mouse model of PD. Young transgenic and wild-type mice received an immunisation regimen over a period of 6 weeks, then observed for an additional 9 weeks. Behavioural assessment was conducted before immunisation and at 15 weeks after the first dose. UB-312 immunisation prevented the development of motor impairment in the wire test and challenging beam test, which was associated with reduced levels of αSyn oligomers in the cerebral cortex, hippocampus and striatum of Thy1SNCA/15 mice. UB-312 immunotherapy resulted in a significant reduction of theαSyn load in the colon, accompanied by a reduction in enteric glial cell reactivity in the colonic ganglia. Our results demonstrate that immunisation with UB-312 prevents functional deficits and both central and peripheral pathology in Thy1SNCA/15 mice.
Animals, Brain/pathology, Disease Models, Animal, Humans, Intestines/pathology, Mice, Mice, Transgenic, Parkinsonian Disorders/pathology, Protein Aggregation, Pathological/prevention & control, Vaccination/methods, Vaccines, Subunit/pharmacology, alpha-Synuclein/antagonists & inhibitors
55-73
Nimmo, Jacqui T
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Smith, Harry
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Wang, Chang Yi
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Teeling, Jessica L
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Nicoll, James A R
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Verma, Ajay
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Dodart, Jean-Cosme
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Liu, Zhi
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Lin, Feng
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Carare, Roxana O
0478c197-b0c1-4206-acae-54e88c8f21fa
1 January 2022
Nimmo, Jacqui T
222608e3-256e-4ba4-a259-cbdfcb5340c6
Smith, Harry
b7d96200-8d79-4289-bd65-18474c162b68
Wang, Chang Yi
5f7b1b38-4008-4e34-aeb4-ef23a5b85356
Teeling, Jessica L
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Nicoll, James A R
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Verma, Ajay
87adfc69-4702-4792-8a59-5aa007e47427
Dodart, Jean-Cosme
042937d4-d3a6-4e37-9274-d1b90ee33c59
Liu, Zhi
c80960b9-c0eb-4f28-b96f-818d8aef3154
Lin, Feng
9067ee54-a57f-4432-b390-ec81fd8aa73c
Carare, Roxana O
0478c197-b0c1-4206-acae-54e88c8f21fa
Nimmo, Jacqui T, Smith, Harry, Wang, Chang Yi, Teeling, Jessica L, Nicoll, James A R, Verma, Ajay, Dodart, Jean-Cosme, Liu, Zhi, Lin, Feng and Carare, Roxana O
(2022)
Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut.
Acta Neuropathologica, 143 (1), .
(doi:10.1007/s00401-021-02381-5).
Abstract
Alpha synuclein has a key role in the pathogenesis of Parkinson's disease (PD), Dementia with Lewy Bodies (LBD) and Multiple System Atrophy (MSA). Immunotherapies aiming at neutralising toxic αSyn species are being investigated in the clinic as potential disease modifying therapies for PD and other synucleinopathies. In this study, the effects of active immunisation against αSyn with the UB-312 vaccine were investigated in the Thy1SNCA/15 mouse model of PD. Young transgenic and wild-type mice received an immunisation regimen over a period of 6 weeks, then observed for an additional 9 weeks. Behavioural assessment was conducted before immunisation and at 15 weeks after the first dose. UB-312 immunisation prevented the development of motor impairment in the wire test and challenging beam test, which was associated with reduced levels of αSyn oligomers in the cerebral cortex, hippocampus and striatum of Thy1SNCA/15 mice. UB-312 immunotherapy resulted in a significant reduction of theαSyn load in the colon, accompanied by a reduction in enteric glial cell reactivity in the colonic ganglia. Our results demonstrate that immunisation with UB-312 prevents functional deficits and both central and peripheral pathology in Thy1SNCA/15 mice.
Text
Nimmo2021_Article_ImmunisationWithUB-312InTheThy (1)
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Published date: 1 January 2022
Additional Information:
Funding Information:
This work has been supported by the Ph.D. studentship from Vaxxinity (Vaxxinity, Dallas Tx, USA).
Publisher Copyright:
© 2021, The Author(s).
Keywords:
Animals, Brain/pathology, Disease Models, Animal, Humans, Intestines/pathology, Mice, Mice, Transgenic, Parkinsonian Disorders/pathology, Protein Aggregation, Pathological/prevention & control, Vaccination/methods, Vaccines, Subunit/pharmacology, alpha-Synuclein/antagonists & inhibitors
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Local EPrints ID: 452682
URI: http://eprints.soton.ac.uk/id/eprint/452682
ISSN: 0001-6322
PURE UUID: 163909ab-6520-47ff-b3bf-2035eba770de
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Date deposited: 11 Dec 2021 11:36
Last modified: 17 Mar 2024 03:00
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Contributors
Author:
Jacqui T Nimmo
Author:
Harry Smith
Author:
Chang Yi Wang
Author:
Ajay Verma
Author:
Jean-Cosme Dodart
Author:
Zhi Liu
Author:
Feng Lin
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