Methods and compositions for monitoring progression of huntington's disease
The invention relates to a method of diagnosis of Huntington's Disease in a diagnostic sample of a valid body tissue taken from a human subject, which comprises detecting an altered concentration of a protein in the diagnostic sample, compared with a sample of a control human subject, the protein being selected from: Swiss Prot accession number: Protein name; P10909: Clusterin precursor; P00738: Haptoglobin precursor; P01009: Alpha-1-antitrypsin precursor; P01024: Complement C3 precursor; P01620: 1g kappa chain V-III region; P01834: 1 g kappa chain C region P01842: 1g lambda chain C regions; P01857: 1g gamma-1 chain C region; P01859: Ig gamma-2 chain C region; P01876: 1g alpha-1 chain C region P02647: Apolipoprotein A-I precursor; P02649: Apolipoprotein E precursor; P02652: Apolipoprotein A-II precursor; P02655: Apolipoprotein C-II precursor; P02656: Apolipoprotein C-II precursor P02671: Fibrinogen alpha/alpha-E chain precursor; P02763: Alpha-1-acid glycoprotein 1 precursor; P02766: Transthyretin precursor; P02768: Serum albumin precursor; P02787: Serotransferrin precursor; P04196: Histidine-rich glycoprotein precursor; P06727: Apolipoprotein A-IV precursor; P19652: Alpha-1-acid glycoprotein 2 precursor; P68871/P02042: Hemoglobin beta chain/Hemoglobin delta chain; P60709: Beta actin.
1. A method for monitoring the progression of Huntington's Disease in a diagnostic sample of a valid body tissue taken from a living human subject having Huntington's Disease, which comprises
detecting the concentration of Clusterin precursor (SwissProt Acc. No, P10909) in the diagnostic sample, and comparing it with the concentration of Clusterin precursor in an earlier sample from the same subject or with a standard value typical of a stage of the disease; and
determining the progression of Huntington's disease in the human subject based on the comparison,
wherein the progression of Huntington's Disease is monitored up to the moderate stage.
2. A method according to claim 1 , which comprises detecting an increased concentration of Clusterin precursor in the diagnostic sample, compared with an earlier sample from the same subject.
3. A method according to claim 1 or 2 , wherein the detection is performed on the diagnostic sample by a binding assay for the Clusterin precursor.
4. A method according to claim 3 , wherein the binding assay comprises causing the Clusterin precursor of the diagnostic sample to interact with a specific binding partner and detecting the interaction.
5. A method according to claim 4 , wherein the specific binding partner is a labelled antibody that recognizes the Clusterin precursor.
6. A method according to claim 5 , wherein the antibody is immobilized on a solid phase.
7. A method according to claim 5 , wherein the antibody is immobilized on beads or on a chip.
8. A method according to claim 1 or 2 , wherein the diagnostic sample is subjected to two dimensional gel electrophoresis to yield a stained gel and an altered concentration of the Clusterin precursor is detected by an increased or decreased intensity of a protein-containing spot on the stained gel, compared with a corresponding control gel.
9. A method according to claim 1 or 2 , wherein the valid body tissue is a body fluid.
10. A method according to claim 1 or 2 , wherein the valid body tissue is of brain or nerve tissue.
11. A method according to claim 1 or 2 , wherein a particular stage of Huntington's disease is diagnosed.
12. A method according to claim 11 , wherein the progression of Huntington's disease in a subject is monitored by carrying out diagnoses on samples taken at intervals from the same subject.
13. A method according to claim 11 , wherein an increased level of clusterin precursor compared to the previous level in an earlier sample from the same individual indicates an increase in severity of disease.
14. A method according to claim 11 , wherein the progression of Huntington's disease in a subject is monitored by measuring the level of clusterin precursor (SwissProt Ace. No. P10909), and optionally an additional protein selected from the group consisting of apolipoprotein A-IV precursor (SwissProt Ace, No. P06727), beta actin (SwissProt Ace. No. P60709), and combinations thereof, whereby an increased level of one or more of these proteins compared to the respective previous level of the one or more proteins in an earlier sample from the same individual indicates an increase in severity of disease.
15. A method according to claim 11 , wherein the monitoring of the progression of Huntington's disease is used to monitor the efficacy of treatment.
16. A method according to claim 1 or 2 , wherein another disease, which may or may not be neurological, is diagnosed in the same sample of body tissue, by a method which comprises detecting an increased concentration of another protein in the diagnostic sample, compared with a sample of a control, normal human subject.