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ABBV-0805, a novel ...
ABBV-0805, a novel antibody selective for soluble aggregated alpha-synuclein, prolongs lifespan and prevents buildup of alpha-synuclein pathology in mouse models of Parkinson's disease
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- Nordström, Eva (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Eriksson, Fredrik (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Sigvardson, Jessica (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Johannesson, Malin (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Kasrayan, Alex (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Jones-Kostalla, Martina (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Appelkvist, Paulina (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Söderberg, Linda (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Nygren, Patrik (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Blom, Magdalena (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Rachalski, Adeline (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Nordenankar, Karin (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Zachrisson, Olof (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Amandius, Ebba (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Osswald, Gunilla (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Moge, Mikael (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik
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- Bergström, Joakim (författare)
- Uppsala universitet,Geriatrik
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- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik,BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Möller, Christer (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Giorgetti, Marco (författare)
- AbbVie Inc, 1 Waukegan Rd, N Chicago, IL 60064 USA.
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- Fälting, Johanna (författare)
- BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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BioArct AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden Geriatrik (creator_code:org_t)
- Elsevier, 2021
- 2021
- Engelska.
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Ingår i: Neurobiology of Disease. - : Elsevier. - 0969-9961 .- 1095-953X. ; 161
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- A growing body of evidence suggests that aggregated alpha-synuclein, the major constituent of Lewy bodies, plays a key role in the pathogenesis of Parkinson's disease and related alpha-synucleinopathies. Immunotherapies, both active and passive, against alpha-synuclein have been developed and are promising novel treatment strategies for such disorders. Here, we report on the humanization and pharmacological characteristics of ABBV-0805, a monoclonal antibody that exhibits a high selectivity for human aggregated alpha-synuclein and very low affinity for monomers. ABBV-0805 binds to a broad spectrum of soluble aggregated alpha-synuclein, including small and large aggregates of different conformations. Binding of ABBV-0805 to pathological alpha-synuclein was demonstrated in Lewy body-positive post mortem brains of Parkinson's disease patients. The functional potency of ABBV-0805 was demonstrated in several cellular assays, including Fc gamma-receptor mediated uptake of soluble aggregated alpha-synuclein in microglia and inhibition of neurotoxicity in primary neurons. In vivo, the murine version of ABBV-0805 (mAb47) displayed significant dose dependent decrease of alpha-synuclein aggregates in brain in several mouse models, both in prophylactic and therapeutic settings. In addition, mAb47 treatment of alpha-synuclein transgenic mice resulted in a significantly prolonged survival. ABBV-0805 selectively targets soluble toxic alpha-synuclein aggregates with a picomolar affinity and demonstrates excellent in vivo efficacy. Based on the strong preclinical findings described herein, ABBV-0805 has been progressed into clinical development as a potential disease-modifying treatment for Parkinson's disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Parkinson's disease
- alpha-Synuclein
- Humanized monoclonal antibody
- Immunotherapy
- Clinical development
- ABBV-0805
- mAb47
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Nordström, Eva
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Eriksson, Fredri ...
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Sigvardson, Jess ...
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Johannesson, Mal ...
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Kasrayan, Alex
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Jones-Kostalla, ...
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visa fler...
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Appelkvist, Paul ...
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Söderberg, Linda
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Nygren, Patrik
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Blom, Magdalena
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Rachalski, Adeli ...
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Nordenankar, Kar ...
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Zachrisson, Olof
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Amandius, Ebba
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Osswald, Gunilla
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Moge, Mikael
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Ingelsson, Marti ...
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Bergström, Joaki ...
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Lannfelt, Lars
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Möller, Christer
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Giorgetti, Marco
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Fälting, Johanna
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Neurobiology of ...
- Av lärosätet
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Uppsala universitet