Objective: We report on the pharmacological characteristics of ABBV-0805 (BAN0805), a monoclonal antibody that exhibits a high selectivity for human α-synuclein oligomers and very low affinity for monomers.

Background: A growing body of evidence suggests that aggregated α-synuclein, the major constituent of Lewy bodies, plays a key role in the pathogenesis of Parkinson’s disease and related α-synucleinopathies. Immunotherapy against α-synuclein has been developed and is a promising novel treatment strategy for such disorders.

Method: SPR, ELISA and IHC was used to characterize ABBV-0805 target binding. In vivo efficacy was assessed in α-synuclein transgenic mice.

Results: ABBV-0805 binds to a broad spectrum of soluble aggregated α-synuclein, including small and large aggregates of different conformations.
Binding of ABBV-0805 to pathological α-synuclein was demonstrated in Lewy body-positive post mortem brains of Parkinson’s disease patients.
In α-synuclein transgenic mice, the murine version of ABBV-0805 displayed significant dose-dependent reduction of both soluble and insoluble α-synuclein aggregates in brain and prolonged lifespan.

Conclusion: ABBV-0805 selectively targets soluble toxic α-synuclein oligomers with a high affinity and demonstrates excellent in vivo efficacy. Based on the strong preclinical findings, ABBV-0805 has been progressed into clinical development as a potential disease-modifying treatment for Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/abbv-0805-a-novel-%ce%b1-synuclein-oligomer-selective-antibody-prolonged-lifespan-and-prevented-accumulation-of-%ce%b1-synuclein-pathology-in-mouse-models-of-parkinsons-disease/