Antibodies and vaccines for use in therapeutic and diagnostic methods for α-synuclein-related disorders

Inventors

Lannfelt, Lars • Bergström, Joakim • Ingelsson, Martin • Gellerfors, Pär

Assignees

Bioarctic AB

Abstract

A vaccine for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual comprises a therapeutically effective amount of isolated stabilized soluble α-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized oligomer of the α-synuclein. An antibody for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual binds soluble α-synuclein. Methods for delaying an onset of for treatment or for prevention of an α-synuclein-related disorder employ the vaccine or antibody. Methods of detecting α-synuclein oligomers employ the antibody.

Core Innovation

The document concerns antibodies and vaccines for α-synuclein-related disorders. It addresses α-synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies, which are associated with Lewy bodies and Lewy neurites. The disclosed concept uses stabilized soluble α-synuclein oligomers as vaccine antigens and antibody targets.

Stabilized soluble α-synuclein oligomers are characterized as forming non-soluble aggregated forms more slowly than non-stabilized soluble oligomers. The stabilized soluble oligomers include soluble α-synuclein oligomers such as protofibrils, and are presented as antigens capable of generating antibodies that bind soluble α-synuclein, including soluble oligomers and stabilized soluble α-synuclein oligomer complexes.

The document further describes diagnostic detection using antibodies that bind stabilized soluble α-synuclein oligomer forms. It includes in vitro and in vivo detection approaches based on detecting and measuring complexes between the antibody and soluble α-synuclein oligomer complexes in a biological sample. Stabilization modalities described include covalent modification with hydrophobic organic aldehydes such as HNE and ONE, other hydrophobic agents or detergents or bile acid derivatives, natural biomolecule stabilizers, and protein cross-linking agents.

Claims Coverage

Two independent claims are present. Each independent claim centers on stabilized soluble α-synuclein oligomers with a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer, together with antibody binding to those stabilized soluble oligomers.

The claim coverage is centered on antibodies that bind stabilized soluble α-synuclein oligomers with a lower formation rate to a non-soluble aggregated form than non-stabilized soluble oligomers.

Stated Advantages

Documented Applications