ALPHA-SYNUCLEIN ANTIBODIES AND USES THEREOF
The invention describes antibodies having a high affinity for aggregated forms of α-synuclein and a low affinity for monomeric forms of α-synuclein. The antibodies are useful in the diagnosis of neurodegenerative diseases.
1 . An antibody or fragment thereof having high affinity for α-synuclein aggregates and low affinity binding for synuclein monomers.
2 . An antibody or fragment thereof according to claim 1 wherein the α-synuclein aggregates comprise protofibrils and/or soluble oligomers of α-synuclein.
3 . An antibody or fragment thereof according to claim 1 wherein the α-synuclein aggregates comprise α-synuclein fibrils.
4 . An antibody or fragment thereof according to claim 1 wherein the antibody or fragment thereof has a dissociation constant, Kd, of less than 10 −7 M for human α-synuclein aggregates.
5 . An antibody or fragment thereof according to claim 1 wherein the antibody or fragment thereof has a dissociation constant, Kd, of more than 10 −5 M for monomeric α-synuclein.
6 . Antibody or fragment thereof according to claim 1 wherein the antibody has a higher affinity for α-synucleins fibrils than for oligomeric forms of α-synucleins.
7 . An antibody or fragment thereof according to claim 1 wherein the antibody or fragment thereof binds to an epitope comprising a C-terminal region of α-synuclein.
8 . An antibody or fragment thereof according to claim 1 wherein the antibody or fragment thereof is a confirmational antibody.
9 . An antibody or fragment thereof according to claim 1 wherein the antibody or fragment thereof do not recognise a linear epitope of α-synuclein.
10 . An antibody or fragment thereof according to claim 1 wherein the antibody is a monoclonal antibody.
11 . A pharmaceutical composition comprising an antibody or fragment according to claim 1 and a pharmaceutically acceptable diluent or carrier.
12 . An antibody or fragment according to claim 1 for use as a medicament.
13 . A method for preventing or treating a neurodegenerative disorder with α-synuclein pathology in an individual comprising administration of an antibody or fragment according to claim 1 to the individual.
14 . A method according to claim 13 , wherein the neurodegenerative disorder is Parkinson's disease, dementia with Lewy Bodies, Alzheimer's disease, multiple system atrophy, psychosis, schizophrenia or Creutzfeldt-Jakob disease.
15 . A test kit for use in a method of determining whether or not an individual has a neurodegenerative disease comprising an antibody or fragment thereof according to claim 1 .
16 . A method of detecting α-synuclein fibrils and aggregates comprising the steps of
adding the antibody or fragment according to claim 1 to a biological sample, and
detecting the presence of a complex formed between α-synuclein fibrils and/or aggregates and the antibody or fragment.
17 . A method for diagnosing a neurodegenerative disease associated with α-synuclein comprising:
adding the antibody or fragment according to claim 1 to a biological sample from a subject, and
detecting the presence or absence of a complex formed between α-synuclein aggregates and the antibody or fragment.
18 . An antibody or fragment according to claim 1 for use as an imaging agent.
19 . A method for imaging α-synuclein aggregates comprising
administering the antibody or fragment according to claim 1 to an individual, and
detecting the antibody.
20 . The method according to claim 19 wherein the antibody comprises a detectable label.