Human diseases marker

Many fundamental risk in general medical practices are made by assessment of biomarker. Biomarker is a parameter that can be used to measure the progress of disease or the effects of treatment. The parameter can be chemical, physical or biological. In molecular terms biomarker is "the subset of markers that might be discovered using genomics, proteomics technologies or imaging technologies. Biomarkers plays major role in medicinal biology. Biomarker brings the future things in our hand by helping in early diagnosis, disease prevention, drug target identification, drug response etc. Several diseased based biomarker had been identified for many diseases such as serum LDL for cholesterol, blood pressure, P53 gene for cancer etc. Gene based biomarker is found to be an effective and acceptable marker in the present scientific world.

Biomarker classification and application

Biomarkers can be classified based on different parameters. They can be classified based on their characteristics such as imaging biomarkers (CT, PET, MRI) or molecular biomarkers. Molecular biomarkers can be used to refer to nonimaging biomarkers that have biophysical properties, which allow their measurements in biological samples (eg, plasma, serum, cerebrospinal fluid, bronchoalveolar lavage, biopsy) and include nucleic acids-based biomarkers such as gene mutations or polymorphisms and quantitative gene expression analysis, peptides, proteins, lipids metabolites, and other small molecules. Biomarkers can also be classified based on their application such as diagnostic biomarkers (ie, cardiac troponin for the diagnosis of myocardial infarction), staging of disease biomarkers (ie, brain natriuretic peptide for congestive heart failure), disease prognosis biomarkers (cancer biomarkers), and biomarkers for monitoring the clinical response to an intervention (HbAlc for antidiabetic treatment). Another category of biomarkers includes those used in decision making in early drug development. For instance, pharmacodynamic (PD) biomarkers are markers of a certain pharmacological response, which are of special interest in dose optimization studies.

Discovery of molecular biomarker

Molecular biomarkers have been defined as biomarkers that can be discovered using basic and acceptable platforms such as genomics and proteomics [9] .Many genomic and proteomics techniques are available for biomarker discovery and few recently using techniques are given below. Apart from genomics and proteomics platforms biomarker assay techniques. Metabolomics, Lipidomics, and Glycomics are also the most commonly used as techniques in identification of biomarker.

Genomic Approach

1.Northern blot

2.Gene expression

3.SAGE

4.DNA Microarray

Proteomic Approach

1.2D-PAGE

2.LS/MS

3.SELDI-TOF

4.Ab Microarray

5.Tissue Microarray

Metabolomics Approach

The term metabolomics has been recently introduced to address the global analysis of all metabolites in a biological sample. A related term, metabonomics, was introduced to refer specifically to the analysis of metabolic responses to drugs or diseases. Metabonomics become a major area of research it is the complex system biological study,used as a to identify the biomarker for various disease. In general most of the disease case some of the metabolic pathway had been activate or deactivated,this parameter can be used as a marker for some diseases. Serotonin production pathway activated in alcoholic drinking person it can be metabolic marker of recent alcohol consumption.

Lipidomics Approach

Lipidomics refers to the analysis of lipids. Since lipids have unique physical properties, they have been traditionally difficult to study. However, improvements in new analytical platforms have made it possible to identify and to quantify most of lipids metabolites from a single sample. Three key platforms used for lipid profiling include mass spectrometry, chromatography, and nuclear magnetic resonance.Mass spectrometry was used to delineate the relative concentration and composition of high-density lipoproteins (HDL) particles from lipid extracts isolated from coronary bypass patients and healthy volunteers. They found that HDL particles from coronary bypass patients contained significantly less sphingomyelin relative to phosphadidylcholine and higher triglycerides relative to cholesterol esters.Lipidomic profiling was also used to study the effect of rosiglitazone, a PPARγ agonist, on lipid metabolism on mice. Rosiglitazone was observed to alter lipid composition in different organs. It increased triglycérides accumulation in the liver; altered free fatty acids in the heart, in the adipose tissue, and in the heart; and reduced triglyceride levels in plasma.

Molecular biomarker in drug development

Some of the main areas in which molecular biomarkers are used in the drug development process are

(1) Early drug development studies

(2) Safety studies

(3) Proof of concept studies

(4) Molecular profiling

Molecular biomarkers are often used in early drug development studies. For instance, they are used in phase I study for establishing doses and dosing regimen for future phase II studies. PD biomarkers are commonly observed to respond (either decrease or increase) proportionally with dose. This data, in conjunction with safety data, help determine doses for phase II studies. In addition, Safety molecular biomarkers have been used for decades both in preclinical and clinical research. Since these tests have become mainstream tests, they have been fully automated for both animal and human testing. Among the most common safety tests are those of liver function(eg, transaminases, bilirubin, alkaline phosphatase) and kidney function(eg, serum creatinine, creatinine clearance, cystatin C). Others include markers of skeletal muscle(eg, myoglobin) or cardiac muscle injury(eg, CK-MB, troponin I or T), as well as bone biomarkers(eg, bone-specific alkaline phosphatase).

Author

S.S.J.Shiek Fareeth Ahmed,T.Hema Thanka Chirstlet,Dept Biotechnology, SRM University,Kattankulathur.