SYNTHETIC BLOOD VESSELS AND USES THEREOF

• US 20180275147A1
• Filed: 03/26/2018
• Published: 09/27/2018
• Est. Priority Date: 03/24/2017
• Status: Active Grant

• Current Assignee: University of British Columbia
• Original Assignee: University of British Columbia
• Inventors: WELLINGTON, CHERYL, ROBERT, JEROME
• Granted Patent: US 10,451,637 B2
• Time in Patent Office: Days
• CPC Class Codes: G01N 2333/4709 Amyloid plaque core protein
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 2800/2871 Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 33/5058 Neurological cells
• CPC Class Codes: G01N 33/5061 Muscle cells
• CPC Class Codes: G01N 33/5064 Endothelial cells
• CPC Class Codes: G01N 33/5082 Supracellular entities, e.g. tissue, organisms
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The present invention provides a synthetic blood vessel and use thereof in drug screening, drug delivery and prognoses of cerebrovascular dysfunction.

Claims

1. A method of identifying an amyloid beta (Aβ

) modulator, the method comprising;

i) providing a synthetic blood vessel,

ii) providing an Aβ

peptide;

iii) providing a test compound;

iv) contacting the synthetic blood vessel with the Aβ

peptide;

v) contacting the synthetic blood vessel with the test compound; and

vi) determining the level of Aβ

deposition or transport, wherein the test compound is an Aβ

modulator if it inhibits Aβ

deposition or enhances Aβ

transport.

2. The method of claim 1 further comprising contacting the synthetic blood vessel with a lipoprotein.

3. The method of claim 2 wherein the lipoprotein is an apolipoprotein or a high-density lipoprotein (HDL)

4. The method of claim 3 wherein the apolipoprotein is an apoE isoform.

5. The method of claim 2 wherein the lipoprotein is from an astrocyte, unfractionated plasma or serum.

6. The method of claim 1 wherein the Aβ

peptide is an Aβ

40 peptide or an Aβ

42 peptide.

7. The method of claim 1 wherein the Aβ

peptide is from a neuronal cell.

8. The method of claim 1 wherein the test compound is added prior to the addition of the Aβ

peptide;

simultaneously with the Aβ

peptide;

or subsequent to the addition of the Aβ

peptide.

9. The method of claim 1 wherein the synthetic blood vessel is a bipartite vessel, a tripartite vessel, a quadripartite vessel or a pentapartite vessel.

10. The method of claim 1 wherein the synthetic blood vessel is coupled to a fluid flow system.

11. The method of claim 1 wherein the determining is done by an immunological assay or a microscopy assay.

13. The method of claim 11 further comprising monitoring the risk for the cerebrovascular dysfunction.

14. The method of claim 11 wherein the sample comprises HDL or apoE or a combination thereof.

15. The method of claim 13 further comprising providing a monocyte cell and determining the level of monocyte adhesion.

16. The method of claim 14 further comprising determining the level of endothelial cell activation.

17. The method of claim 11 wherein the cerebrovascular dysfunction is type II diabetes mellitus, hypercholesterolemia, hypertension, cerebral amyloid angiopathy (CAA), ischemic brain injury, stroke, dementia, cognitive impairment and Alzheimer'"'"'s disease.

18. The method of claim 11 wherein the subject is a human.

12. A method of determining the risk for a cerebrovascular dysfunction in a subject in need thereof comprising:

i) providing a synthetic blood vessel;

ii) providing an Aβ

peptide;

iii) contacting the synthetic blood vessel with a sample from the subject; and

iv) determining the level of Aβ

deposition or transport in the sample, wherein the subject has an increased risk for a cerebrovascular dysfunction if the level of Aβ

deposition is increased or if Aβ

transport is reduced.

19. A method of determining whether a compound is suitable for delivery to the brain, comprising:

i) providing a synthetic blood vessel, wherein the synthetic blood vessel is at least a tripartite vessel;

i) contacting the lumen of the synthetic blood vessel with a test compound;

ii) determining the level of transport of the test compound to the antelumen of the tripartite vessel,

wherein the test compound is suitable for delivery to the brain if it is transported to the antelumen of the tripartite vessel.

20. A synthetic blood vessel kit comprising:

i) a synthetic blood vessel; and

ii) an amyloid beta (Aβ

) peptide, together with instructions for use, wherein the synthetic blood vessel kit optionally further comprises a lipoprotein or a monocytic cell or a combination thereof.