GM1 ganglioside to annexin V microparticle polypeptide ratio for biological monitoring

Patent metadata

Field	Value
Publication number	US-9423402-B2
Application number	US-201214361500-A
Country	US
Kind code	B2
Filing date	Nov 30, 2012
Priority date	Nov 30, 2011
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

Abstract

We describe a method of monitoring the state of a cell, tissue, organ or organism. The method comprises establishing, for a sample of microparticles from the cell, tissue, organ or organism, a ratio. The ratio is of a selected polypeptide in microparticles which comprise GM1 gangliosides, preferably which bind to Cholera Toxin B (CTB) (“GM1 ganglioside microparticle polypeptide”) to the selected polypeptide in microparticles which comprise exposed phosphotidylserine, preferably which bind to Annexin V (“Annexin V microparticle polypeptide”). The GM1 ganglioside microparticle polypeptide to Annexin V microparticle polypeptide ratio so established may be indicative of the state of the cell, tissue, organ or organism.

First claim

The invention claimed is:

1. A method of monitoring the state of a cell, tissue, organ or organism, and treating a cardiovascular disease state, the method comprising establishing, for a sample of microparticles from the cell, tissue, organ or organism, a ratio of:
(i) (a) a selected polypeptide in microparticles which comprise GM1 gangliosides to
(b) the selected polypeptide in microparticles which comprise exposed phosphotidylserine wherein the (a) to (b) ratio is indicative of the state of the cell, tissue, organ or organism
(ii) wherein if the ratio of (a) to (b) is higher in the sample of microparticles relative to a control sample, administering a cardiovascular disease treatment to the cell, tissue, organ or organism.

2. The method of claim 1 , further comprising a step of selecting microparticles by size or which comprises establishing a profile comprising a plurality of GM1 ganglioside microparticle polypeptide to Annexin V microparticle ratios for a plurality of selected polypeptide species.

3. The method of claim 1 , wherein the cardiovascular disease state comprises a Chronic Heart Failure disease state or an Acute Myocardial Ischemia (AMI) state, or a pre-eclampsia state.

4. The method of claim 1 , wherein the state of the cell, tissue, organ, or organism comprises a pre-eclampsia state and wherein the polypeptide comprises one or a combination of PAI-1, PLGF, Pro-calcitonin, S100b, TGFβ, or TIMP-1.

5. The method of claim 1 , wherein
(a) the microparticles comprise CD9+ microparticles;
(b) the microparticles comprise microvesicles, exosomes, ectosomes or apoptotic bodies;
(c) the state of the cell, tissue, organ or organism comprises a physiological state, a differentiation state, a development state or a metabolic state or a pathological state, a disease state, a human disease state, a food poisoning state, a diabetic state, an immune disorder state, a neurodegenerative disorder state, an oncogenic state, a cancerous state or a tumour state;
(d) the state of the cell, tissue, organ or organism comprises a state of being sick, a state of poor prognosis, a state of recovery from sickness, a state of good prognosis or a healthy state;
(e) the sample is selected from the group consisting of: urine, blood, tears, saliva, bronchoaveolar fluid, tumoral effusions, epididymal fluid, amniotic fluid and milk; or
(f) any combination of the above.

6. The method of claim 1 , which further comprises a step of normalising the level, concentration or amount of the selected polypeptide between two or more samples, in which the normalisation is conducted with reference to BNP, CD9 and/or TIMP-1 polypeptide.

7. The method of claim 1 , wherein the microparticles which comprise GM1 gangliosides bind to Cholera Toxin B (CTB) and/or wherein the microparticles which comprise exposed phosphotidylserine bind to Annexin V.

8. The method of claim 1 , wherein the selected polypeptide is CD9.

Assignees

• Agency Science Tech & Res
• Singapore Health Serv Pte Ltd
• Singapore Health Serv Pte Ltd
• Agency For Science Tech And Res (A*Star)

Inventors

• Lim Sai Kiang
• Tan Kok Hian

Classifications

• G01N2800/32

  Cardiovascular disorders · CPC title

• G01N33/6872 Primary

  Intracellular protein regulatory factors and their receptors, e.g. including ion channels · CPC title

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title

• G01N2333/47

  Assays involving proteins of known structure or function as defined in the subgroups · CPC title

• G01N2800/7028

  Cancer · CPC title