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  1. Article ; Online: Correction: Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy.

    Nimmo, Jacqui T / Verma, Ajay / Dodart, Jean-Cosme / Wang, Chang Yi / Savistchenko, Jimmy / Melki, Ronald / Carare, Roxana O / Nicoll, James A R

    Alzheimer's research & therapy

    2023  Volume 15, Issue 1, Page(s) 18

    Language English
    Publishing date 2023-01-21
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2506521-X
    ISSN 1758-9193 ; 1758-9193
    ISSN (online) 1758-9193
    ISSN 1758-9193
    DOI 10.1186/s13195-022-01156-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy.

    Nimmo, Jacqui T / Verma, Ajay / Dodart, Jean-Cosme / Wang, Chang Yi / Savistchenko, Jimmy / Melki, Ronald / Carare, Roxana O / Nicoll, James A R

    Alzheimer's research & therapy

    2020  Volume 12, Issue 1, Page(s) 159

    Abstract: Background: Alpha-synuclein (α-Syn) aggregation is the primary characteristic of synucleinopathies including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Immunotherapy targeting α-Syn has shown promising ... ...

    Abstract Background: Alpha-synuclein (α-Syn) aggregation is the primary characteristic of synucleinopathies including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Immunotherapy targeting α-Syn has shown promising results in animal models of the disease. This study investigates the target specificity of three different active vaccines for pathological α-Syn aggregates found in human brain tissue from synucleinopathies.
    Methods: Guinea pigs were immunised with 3 vaccines developed by United Neuroscience, and IgG fractions purified from the resulting immune sera (IGG-1, IGG-2 or IGG-3) were used to perform immunohistochemical staining of human cases of PD, DLB and MSA. The resulting immunoreactivity was compared to a commercially available α-Syn antibody from Novacastra (NOV) commonly used for diagnostic purposes. Images were captured from the substantia nigra (SN), temporal lobe, internal capsule, insular cortex and putamen and quantified for the percentage area with α-Syn immunoreactivity. Lewy bodies (LB) and Lewy neurites (LN) were further analysed in PD and DLB cases.
    Results: Vaccine-generated antibodies detected more α-Syn pathology compared to NOV. The levels of α-Syn immunoreactivity varied between brain region and disease type with IGG-3 recognising the highest levels of α-Syn in most cases and in all brain regions that are affected early in disease progression. IGG-3 had a high recognition for glial inclusions found in MSA which are known to have a more compact conformation. Slot blot analysis confirmed the specificity of IGG-3 for native oligomers and fibrillar α-Syn. Higher levels of α-Syn were recognised by IGG-2 in cortical regions, and by IGG-3 in SN of PD and DLB cases. This was due to increased immunolabelling of LNs in these brain regions suggesting that IGG-2 and IGG-3 recognised additional α-Syn pathology compared to IGG-1 and NOV. Whether the unique binding properties of the antibodies produced in guinea pigs will translate in the clinic remains to be addressed, which is the main limitation of this study.
    Conclusions: These vaccines induce antibodies that bind α-Syn oligomers and aggregates in the human brain and specifically support the choice of the vaccine generating IGG-3 (i.e. UB-312) as a candidate for clinical trials for synucleinopathies.
    MeSH term(s) Animals ; Brain/metabolism ; Guinea Pigs ; Immunotherapy ; Lewy Body Disease/therapy ; Multiple System Atrophy/therapy ; Parkinson Disease/therapy ; Synucleinopathies ; alpha-Synuclein/metabolism
    Chemical Substances alpha-Synuclein
    Language English
    Publishing date 2020-11-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2506521-X
    ISSN 1758-9193 ; 1758-9193
    ISSN (online) 1758-9193
    ISSN 1758-9193
    DOI 10.1186/s13195-020-00727-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut.

    Nimmo, Jacqui T / Smith, Harry / Wang, Chang Yi / Teeling, Jessica L / Nicoll, James A R / Verma, Ajay / Dodart, Jean-Cosme / Liu, Zhi / Lin, Feng / Carare, Roxana O

    Acta neuropathologica

    2021  Volume 143, Issue 1, Page(s) 55–73

    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 ...

    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.
    MeSH term(s) 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
    Chemical Substances Vaccines, Subunit ; alpha-Synuclein
    Language English
    Publishing date 2021-11-06
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-021-02381-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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