Therapy Type: Immunotherapy (passive) (timeline)
Target Type: alpha-synuclein
Condition(s): Parkinson's Disease
U.S. FDA Status: Parkinson's Disease (Phase 1)
Company: AbbVie, BioArctic AB
ABBV-0805 is a humanized monoclonal antibody targeting α-synuclein. Genetic and pathology evidence implicate aggregated forms of this protein in the molecular pathogenesis of Parkinson’s disease and other α-synucleinopathies such as dementia with Lewy bodies (DLB). In 2018, AbbVie licensed this and similar antibodies from the Swedish company BioArctic, and is developing it for the treatment of PD.
BioArctic engineered several antibodies that bind oligomeric/protofibrillar α-synuclein with nanomolar affinity and high selectivity over monomeric protein. No preclinical work has been published on ABBV-0805 by name; however, BioArctic has shown its antibodies reduce pathological α-synuclein protein levels in mice expressing human α-synuclein (Lindstrom et al, 2014; Kallab et al., 2018).
In March 2019, AbbVie began a Phase 1 study of ABBV-0805 in healthy volunteers in the United States (press release). No results are publicly available.
In March 2020, the company started a multicenter, placebo-controlled Phase 1 study in idiopathic, mild to moderate Parkinson’s. It will randomize 32 patients to three escalating doses of antibody or placebo, delivered by intravenous infusion every 28 days. A fourth dose may be added pending initial results. Primary outcomes are number of people with adverse events, and pharmacokinetics of antibody in blood and cerebrospinal fluid. The trial will end in November 2021.
For details on ABBV0805 trials, see clinicaltrials.gov.
Last Updated: 19 Mar 2020
- Lindström V, Fagerqvist T, Nordström E, Eriksson F, Lord A, Tucker S, Andersson J, Johannesson M, Schell H, Kahle PJ, Möller C, Gellerfors P, Bergström J, Lannfelt L, Ingelsson M. Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice. Neurobiol Dis. 2014 Sep;69:134-43. Epub 2014 May 20 PubMed.
- Kallab M, Herrera-Vaquero M, Johannesson M, Eriksson F, Sigvardson J, Poewe W, Wenning GK, Nordström E, Stefanova N. Region-Specific Effects of Immunotherapy With Antibodies Targeting α-synuclein in a Transgenic Model of Synucleinopathy. Front Neurosci. 2018;12:452. Epub 2018 Jul 4 PubMed.
- Gustafsson G, Eriksson F, Möller C, da Fonseca TL, Outeiro TF, Lannfelt L, Bergström J, Ingelsson M. Cellular Uptake of α-Synuclein Oligomer-Selective Antibodies is Enhanced by the Extracellular Presence of α-Synuclein and Mediated via Fcγ Receptors. Cell Mol Neurobiol. 2016 Mar 10; PubMed.
- Almandoz-Gil L, Lindström V, Sigvardson J, Kahle PJ, Lannfelt L, Ingelsson M, Bergström J. Mapping of Surface-Exposed Epitopes of In Vitro and In Vivo Aggregated Species of Alpha-Synuclein. Cell Mol Neurobiol. 2016 Dec 27; PubMed.
- Gustafsson G, Lindström V, Rostami J, Nordström E, Lannfelt L, Bergström J, Ingelsson M, Erlandsson A. Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes. J Neuroinflammation. 2017 Dec 11;14(1):241. PubMed.