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Methods for drug discovery, disease treatment, and diagnosis using metabolomics

a technology of metabolomics and drug discovery, applied in the direction of biochemistry apparatus and processes, instruments, ict adaptation, etc., can solve the problems of expensive and time-consuming procedures, and achieve the effect of accelerating the process of identifying genes

Inactive Publication Date: 2006-06-22
CORNELL RES FOUNDATION INC +1
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Benefits of technology

The patent text describes a method for studying small molecules in cells and organelles, which can help identify potential drug targets and treat disease states. This method involves comparing the small molecule profiles of cells, organelles, or extracellular material with those of healthy individuals or with cells treated with therapeutic agents. The small molecule profiling can also be used to identify individuals from minute biological samples. The invention also includes pharmaceutical compositions and methods for predicting an individual's response to drugs based on their small molecule profile. Overall, this method offers a comprehensive way to study the effects of nongenetic factors on cells and living systems.

Problems solved by technology

For example, once a novel gene or target is discovered by genomics, the investigators must first validate the target using expensive and time consuming procedures which are far removed from the actual disease state.

Method used

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  • Methods for drug discovery, disease treatment, and diagnosis using metabolomics
  • Methods for drug discovery, disease treatment, and diagnosis using metabolomics
  • Methods for drug discovery, disease treatment, and diagnosis using metabolomics

Examples

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example 1

Method for Obtaining a Small Molecule Profile of a Cellular Compartment

[0271] Method for Obtaining a Small Molecule Profile of Mitochondria using HPLC

[0272] The following method demonstrates how small molecules are isolated from mitochondria for methods as described herein.

[0273] Mitochondrial Isolation

[0274] Mitochondria from a mammalian source are isolated by differential centrifugation in 140 mM KCI and 20 mM Hepes, pH 7.4. Following the final wash, mitochondria are resuspended in the same buffer and aliquots are quick frozen in liquid nitrogen. Protein determinations are carried out by Lowry using the Sigma Protein Assay Kit P5656).

[0275] Other mitochondrial samples are purified using a modified version of a published protocol (Rigobello et al. (1995) Arch. Biochem. Biophys. 319, 225-230). Mammalian liver mitochondria are obtained after decapitation of the subjects. The livers are dissected out and are placed in an ice-cold solution containing 250 mM mannitol, 75 mM sucrose...

example 2

Method for Analyzing Metabolic Disorders Using Small Molecule Profiles

[0284] Method for Analyzing Differences in Small Molecule Profiles of Genetically Altered Mice After Short Term Diet Variations

[0285] 15 female C57B1 / 6J ob / ob mice and lean littermate controls (15 female C57B1 / 6J ? / +) and 15 male C57B1 / Ks db / db mice and lean littermate controls (15 male C57B1 / ks + / +) are obtained from Jackson labs at 4.5 weeks of age, and are housed individually on normal mouse chow (West, D. B., 1992, Am. J. Physiol 262:R1025-R1032) for 1 week prior to the initiation of the study. The four groups of 15 mice each are then sacrificed by CO2 euthanasia and tissues are then collected. Body weight (grams) of the four groups of mice at the time of sacrifice are measured. Small molecule profiles from cells from the hypothallumus are then obtained from each group of mice and compared.

[0286] The mice (normal, lean, ob / ob, db / db, and / or tub / tub) are fed normally prior to the initiation of the experimen...

example 3

Comparison of Small Molecule Profiles of Different Types of Immune Cells

[0289] Method for Comparing the Small Molecule Profiles of TH1 and TH2 Cells

[0290] The transgenic T cell example is used to identify cellular small molecules present in TH2 cells. The identified small molecules are be present in different amounts in TH2 cells compared to TH1 cells.

[0291] Transgenic Mice

[0292] Naive CD4+ cells are obtained from the spleens and / or lymph nodes of unprimed transgenic mouse strains harboring a T cell receptor (TCR) recognizing ovalbumin (Murphy et al., 1990, Science 250:1720).

[0293] Ova-Specific Transgenic T Cells

[0294] Suspensions of ova-specific T cells are co-cultured with stimulatory peptide antigen and antigen presenting cells essentially as described in Murphy et al. (Murphy et al., 1990, Science 250:1720). Briefly, 2-4×106 T cells are incubated with approximately twice as many TA3 antigen presenting cells in the presence of 0.3 μM Ova peptide. TH1 cultures may contain ap...

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Abstract

The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy of drugs are also discussed.

Description

RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 10 / 695,265, filed Oct. 27, 2003; which claims priority to U.S. Provisional Patent Application Ser. No. 60 / 421,226, filed on Oct. 25, 2002. U.S. patent application Ser. No. 10 / 695,265, filed Oct. 27, 2003 is also a continuation-in-part of U.S. patent application Ser. No. 09 / 835,119, filed on Apr. 13, 2001; which claims priority to U.S. Provisional Application Ser. No. 60 / 239,340, filed on Oct. 11, 2000; U.S. Provisional Application Ser. No. 60 / 239,541, filed on Oct. 10, 2000; U.S. Provisional Application Ser. No. 60 / 197,117, filed on Apr. 14, 2000; and U.S. Provisional Application Ser. No. 60 / 197,085, filed on Apr. 14, 2000. The entire contents of each of the aforementioned applications are hereby incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] Living organisms are autonomous chemical systems which include diverse sets of small molecules. Small molecules found in liv...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68G01N33/00C12Q1/00
CPCG01N33/5079G01N33/5091G01N33/6893G01N2800/304G01N2800/52G01N33/4833G01N33/5011G01N33/5038Y02A90/10Y02A50/30
Inventor KADDURAH-DAOUK, RIMAKRISTAL, BRUCE
Owner CORNELL RES FOUNDATION INC
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