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

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.

1 . A method for identifying small molecules relevant to a disease state, the method comprising:
 obtaining a small molecule profile of a sample from a subject suffering from said disease state using two or more techniques that detect 50% or more of the small molecules in said sample, said small molecule profile comprising information regarding the presence of two or more types of small molecules selected from the group consisting of: sugars, fatty acids, amino acids, nucleotides, metabolites, and products of catabolism; and   comparing the small molecule profile from said subject to a standard small molecule profile, thereby identifying the small molecules relevant to said disease state using said small molecule profile.   
     
     
         2 . The method of  claim 1 , wherein said subject is a human. 
     
     
         3 . The method of  claim 1 , wherein said subject's small molecule profile is obtained from said subject's tissue or biological fluids. 
     
     
         4 . The method of  claim 3 , wherein said tissue is stomach, colon, skin, breast, muscle, lung, kidney, or liver tissue. 
     
     
         5 . The method of  claim 3 , wherein said tissue comprises a tumor. 
     
     
         6 . The method of  claim 5 , wherein said tumor is malignant. 
     
     
         7 . The method of  claim 1 , wherein said small molecule profile is obtained from said subject's blood, spinal fluid, serum, cells, tissue, or cellular organelles. 
     
     
         8 . The method of  claim 1 , wherein said subject's small molecule profile and said standard small molecule profile are obtained using two or more of the following: HPLC, TLC, electrochemical analysis, mass spectroscopy, refractive index spectroscopy (RI), Ultra-Violet spectroscopy (UV), fluorescence analysis, radiochemical analysis, Near-Infra Red spectroscopy (Near-IR), Nuclear Magnetic Resonance (NMR) and Light Scattering analysis (LS). 
     
     
         9 . The method of  claim 1 , wherein said disease state is an immunological, neurological, metabolic, oncological, viral, or cardiovascular disorder, or a bacterial infection. 
     
     
         10 . The method of  claim 1 , wherein said disease state is a nervous system disorder. 
     
     
         11 . The method of  claim 10 , wherein said nervous system disorder is a neuropathy, Alzheimer disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, acute disseminated encephalomyelitis, acute necrotizing hemorrhagic leukoencephalitis, dysmyelination disease, mitochondrial disease, migrainous disorder, bacterial infection, fungal infection, stroke, aging, dementia, peripheral nervous system diseases, or a mental disorder. 
     
     
         12 . The method of  claim 1 , wherein said disease state is an oncological disorder. 
     
     
         13 . The method of  claim 12 , wherein said oncological disorder is leukemia, brain cancer, pancreatic cancer, prostate cancer, liver cancer, stomach cancer, colon cancer, throat cancer, breast cancer, ovarian cancer, skin cancer, melanoma, lymphoma, or a cancerous tumor. 
     
     
         14 . The method of  claim 12 , wherein said oncological disorder is prostate cancer. 
     
     
         15 . The method of  claim 1 , wherein said disease state is a metabolic disorder. 
     
     
         16 . The method of  claim 15 , wherein said metabolic disorder is diabetes. 
     
     
         17 . The method of  claim 16 , wherein said diabetes is insulin-dependent diabetes. 
     
     
         18 . The method of  claim 15 , wherein said metabolic disorder is a body weight disorder. 
     
     
         19 . The method of  claim 18 , wherein said body weight disorder is obesity, cachexia, or anorexia. 
     
     
         20 . A method for identifying small molecules affected by an agent, the method comprising:
 generating a small molecule profile of a cellular compartment treated with an agent using one or more techniques that detect 50% or more of the small molecules in said sample, said small molecule profile comprising information regarding the presence of two or more types of small molecules selected from the group consisting of: sugars, fatty acids, nucleotides, metabolites, products of catabolism, and amino acids, wherein said cellular compartment is obtained from a patient; wherein said cellular compartment is obtained from a patient; and   comparing said small molecule profile to a standard small molecule profile, thereby identifying the small molecules affected by said agent in said cellular compartment.   
     
     
         21 . The method of  claim 20 , wherein said agent is a toxin. 
     
     
         22 . The method of  claim 20 , wherein said agent is a therapeutic agent. 
     
     
         23 . The method of  claim 22 , wherein said therapeutic agent is a therapeutic agent used for the treatment of a metabolic, immunological, neurological, oncological, viral, or other disorder. 
     
     
         24 . The method of  claim 20 , wherein said patient is suffering from a metabolic, immunological, neurological, oncological, viral, or other disorder. 
     
     
         25 . The method of  claim 20 , wherein said cellular compartment is a cell. 
     
     
         26 . The method of  claim 20 , wherein said cellular compartment is mitochondria. 
     
     
         27 . The method of  claim 20 , wherein said cellular compartment is a nucleus. 
     
     
         28 . The method of  claim 20 , wherein said small molecule profile of a cellular compartment and said standard small molecule profile are obtained using one or more of the following: gas chromatography (GC), HPLC, TLC, electrochemical analysis, mass spectrometry, mass spectroscopy, refractive index spectroscopy (RI), Ultra-Violet spectroscopy (UV), fluorescent analysis, radiochemical analysis, Near-InfraRed spectroscopy (Near-IR), Nuclear Magnetic Resonance spectroscopy (NMR), and Light Scattering analysis (LS). 
     
     
         29 . A method for identifying small molecules affected by an agent comprising:
 generating a small molecule profile of a sample from a human subject treated with an agent using one or more techniques that detect 50% or more of the small molecules in said sample, said small molecule profile comprising information regarding the presence of two or more types of small molecules selected from the group consisting of: sugars, fatty acids, nucleotides, metabolites, products of catabolism and amino acids; and   comparing said small molecule profile to a standard small molecule profile, thereby identifying the small molecules affected by said agent.   
     
     
         30 . The method of  claim 29 , wherein said standard small molecule profile is a profile of said sample from said subject prior to administration of said agent. 
     
     
         31 . The method of  claim 30 , wherein said small molecule profile is obtained from a cell culture. 
     
     
         32 . The method of  claim 30 , wherein said small molecule profile is obtained from a biological fluid of said subject. 
     
     
         33 . The method of  claim 32 , wherein said biological fluid is blood, serum, spinal fluid or saliva. 
     
     
         34 . A method for metabolomically predicting a human's response to a therapeutic agent, the method comprising:
 generating a small molecule profile of a sample from said human using one or more techniques that detect 50% or more of the small molecules in said sample, said small molecule profile comprising information regarding the presence of two or more types of small molecules selected from the group consisting of sugars, fatty acids, nucleotides, metabolites, products of catabolism and amino acids; and   comparing said small molecule profile of said sample from said human to a known standard established for the therapeutic agent as an indication of whether the human would benefit from treatment with the therapeutic agent, said known standard obtained from one or more humans treated with the agent, thereby predicting said human's response to said therapeutic agent.   
     
     
         35 . The method of  claim 34 , wherein said human is suffering or suspected of suffering from a disease state. 
     
     
         36 . The method of  claim 35 , wherein said disease state is an immunological disorder, a neurological disorder, a metabolic disorder, an oncological disorder, a viral disorder, a cardiovascular disorder, or a bacterial infection. 
     
     
         37 . The method of  claim 35 , wherein said disease state is a nervous system disorder. 
     
     
         38 . The method of  claim 37 , wherein said nervous system disorder is a neuropathy, Alzheimer disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, acute disseminated encephalomyelitis, acute necrotizing hemorrhagic leukoencephalitis, dysmyelination disease, mitochondrial disease, migrainous disorder, bacterial infection, fungal infection, stroke, aging, dementia, peripheral nervous system diseases, or a mental disorder. 
     
     
         39 . The method of  claim 34 , wherein said human's small molecule profile is obtained from said human's tissue or biological fluids. 
     
     
         40 . The method of  claim 34 , wherein said human's small molecule profile is obtained from said human's blood, spinal fluid, serum, cells, cellular organelles, urine, interstitial fluid, or saliva. 
     
     
         41 . The method of  claim 34 , wherein said small molecule profile of said sample from said human and said known standard are obtained using one or more of the following: HPLC, TLC, electrochemical analysis, mass spectroscopy, refractive index spectroscopy (RI), Ultra-Violet spectroscopy (UV), fluorescent analysis, radiochemical analysis, Near-InfraRed spectroscopy (Near-IR), Nuclear Magnetic Resonance spectroscopy (NMR), gas chromatography (GC), and Light Scattering analysis (LS). 
     
     
         42 . The method of  claim 34 , wherein said therapeutic agent is an anti-tumor drug. 
     
     
         43 . The method of  claim 34 , wherein said therapeutic agent is administered during clinical trials. 
     
     
         44 . The method of  claim 34 , wherein said therapeutic agent is a peptidomimetic, a protein, a peptide, a small molecule, or a drug candidate.