Theranostics platform and methods of use

Patent metadata

Field	Value
Publication number	US-10161929-B2
Application number	US-201314378283-A
Country	US
Kind code	B2
Filing date	Feb 15, 2013
Priority date	Feb 15, 2012
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

Theranostics platforms for identifying drugs and nutraceuticals for treatment of rare disease are described. The platforms comprise (a) a cell-phenotype image-enhancing instrument; (b) a drug/nutraceutical library; and (c) a computer-implemented system for analyzing a response of an optically-visible rare-disease cell phenotype to a drug or nutraceutical from the drug/nutraceutical library.

First claim

What is claimed is:

1. A disease theranostics platform, comprising:
a. an automated cell-phenotype image-enhancing instrument for detecting an optically-visible disease cell-phenotype which is characterized by abnormal laminin binding, or abnormal lamin A/C or lamin B binding;
b. cells obtained or derived from a subject with the optically-visible disease cell-phenotype characterized by abnormal laminin binding, or abnormal lamin A/C or lamin B binding;
c. a drug/nutraceutical library; and
d. a computer-implemented system for analyzing responses of the optically-visible disease cell-phenotype of the cells obtained or derived from a subject with the optically-visible disease cell-phenotype to drugs or nutraceuticals from the drug/nutraceutical library, wherein the system comprises an algorithm for identifying drugs or nutraceuticals effective for normalizing or partially normalizing the optically-visible disease cell-phenotype.

2. The disease theranostics platform of claim 1 , wherein the automated cell-phenotype image-enhancing instrument is a microscope and detects the response of the optically-visible disease cell-phenotype to a drug or nutraceutical from the drug/nutraceutical library; wherein the microscope comprises:
a. detector for imaging the optically-visible disease phenotype;
b. magnification optics having sufficient magnifying power to visualize one cell in a plurality of cells; and
c. an available electronic memory for storing an image of a cell.

3. The disease theranostics platform of claim 1 , wherein the cells obtained or derived from a subject with the optically-visible disease cell phenotype are differentiated from a stem cell obtained from the subject with the optically-visible disease cell-phenotype, wherein said subject has symptoms of a disease associated with the optically-visible disease cell phenotype, has limited symptoms of the disease associated with the optically-visible disease cell phenotype or is asymptomatic, and the computer-implemented system comprises an algorithm that correlates the optically-visible disease cell-phenotype with the severity of the disease associated with the optically-visible disease cell phenotype in the subject.

4. The disease theranostics platform of claim 1 , wherein the drug/nutraceutical library comprises at least 500 commercially available nutraceuticals, approved therapeutic agents, or combinations thereof.

5. The disease theranostics platform of claim 1 , wherein the computer-implemented system comprises an algorithm that determines degrees of response of the optically-visible disease cell-phenotype to a drug or nutraceutical in the drug/nutraceutical library; and the computer-implemented system correlates the degree of response of the optically-visible disease cell-phenotype to the drug or nutraceutical in the drug/nutraceutical library with an effect of the drug or nutraceutical on at least one symptom of a disease associated with the optically-visible disease cell phenotype in vivo.

6. The disease theranostics platform of claim 1 , further comprising an assay for a biomarker that correlates with the optically-visible disease cell-phenotype, wherein the biomarker is present in blood, plasma, or cell culture medium.

7. The disease theranostics platform of claim 1 , wherein the optically-visible disease cell-phenotype comprises a fluorescent tag.

8. The disease theranostics platform of claim 1 , wherein the optically-visible disease cell-phenotype is cell morphology, nuclear morphology or morphology of any cytosolic organelle.

9. The disease theranostics platform of claim 1 , wherein the optically-visible disease cell-phenotype is associated with a disease, wherein the disease is laminopathy, Fukuyama congenital muscular dystrophy (FCMD), congenital muscular dystrophy unrelated to FCMD, Duchenne muscular dystrophy, Becker's muscular dystrophy, distal muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, Limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, junctional epidermolysis bullosa, or nephrotic syndrome.

10. The disease theranostics platform of claim 1 , wherein the optically-visible disease cell-phenotype is associated with a rare disease, wherein the rare disease affects less than 200,000 persons in a United States population.

11. A method of identifying a drug or nutraceutical candidate for normalizing, or partially normalizing, an optically-visible disease cell phenotype which is characterized by abnormal laminin binding, or abnormal lamin A/C or lamin B binding in a subject in need thereof, comprising the steps of:
a. contacting a plurality of cells with the optically-visible disease cell phenotype with a drug or nutraceutical from a drug/nutraceutical library;
b. using an automated cell-phenotype image-enhancing instrument to obtain a magnified image of the plurality of cells following contact with the drug or nutraceutical from the drug/nutraceutical library, wherein the automated cell-phenotype image-enhancing instrument is configured for detecting the optically-visible disease cell phenotype characterized by abnormal laminin binding, or abnormal lamin A/C or lamin B binding; and
c. using a computer-implemented algorithm to analyze the magnified image to determine the response of the plurality of cells to the drug or nutraceutical from the drug/nutraceutical library;

wherein a drug or nutraceutical that normalizes or partially normalizes the optically-visible disease cell phenotype is identified by the computer-implemented algorithm as a candidate for normalizing, or partially normalizing the optically-visible disease cell phenotype in the subject in need thereof.

12. The method of claim 11 , wherein the subject in need thereof has symptoms of a disease associated with the optically-visible disease cell-phenotype, has limited symptoms of the disease or is asymptomatic.

13. The method of claim 11 , wherein the optically visible disease cell-phenotype is cell morphology, nuclear morphology or morphology of any cytosolic organelle.

14. The method of claim 11 , comprising using a microscope to obtain the magnified image of the plurality of cells.

15. The method of claim 11 , further comprising assaying for a biomarker that correlates with a disease phenotype associated with the optically-visible disease cell-phenotype, wherein the biomarker is present in blood, plasma, or cell culture medium.

16. The method of claim 11 , further comprising contacting the plurality of cells with a fluorescent tag to produce the optically-visible disease cell phenotype.

17. The method of claim 11 , further comprising using a computer-implemented algorithm to correlate the optically-visible disease cell-phenotype with a severity of the optically-visible disease cell-phenotype in vivo.

18. The method of claim 11 , wherein the optically-visible disease cell-phenotype is associated with a disease, wherein the disease is laminopathy, Fukuyama congenital muscular dystrophy(FCMD), congenital muscular dystrophy unrelated to FCMD, Duchenne muscular dystrophy, Becker's muscular dystrophy, distal muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, Limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, junctional epidermolysis bullosa, or nephrotic syndrome.

Assignees

• Sanford Burnham Prebys Medical Discovery Inst
• Sanford Burnham Prebys Medical Discovery

Inventors

• Jackson Michael
• Bang Anne

Classifications

• G01N2800/2878

  Muscular dystrophy · CPC title

• G01N2333/78

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG] · CPC title

• G01N2500/02

  Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor) · CPC title

• G01N2500/10

  involving cells · CPC title

• G01N33/5026 Primary

  on cell morphology · CPC title