The term biomarker, refers to a broad subcategory of medical signs – that is, objective indications of medical state observed from outside the patient – which can be measured accurately and is reproducible.

Ultimately, biomarkers can be used to detect a change in the physiological state of a patient that correlates with the risk or progression of a disease/condition or with the susceptibility of a disease/condition to a given treatment. Biomarkers hold great promise for personalised medicine as information gained from diagnostic or 'progression' markers can be used to tailor treatment to the individual for highly efficient intervention in the disease/condition process.

Better biomarkers are urgently needed to improve diagnosis, guide molecularly targeted therapy and monitor activity and therapeutic response across a wide spectrum of disease. Proteomics methods based on mass spectrometry hold promise for the discovery of novel biomarkers that might form the foundation for new clinical blood tests, but to date their contribution to the diagnostic armamentarium has been disappointing. This is due in part to the lack of a coherent pipeline connecting marker discovery with well-established methods for validation. Advances in methods and technology now enable construction of a comprehensive biomarker pipeline from six essential process components: candidate discovery, qualification, verification, research assay optimisation, biomarker validation and commercialisation. Better understanding of the overall process of biomarker discovery and validation and of the challenges and strategies inherent in each phase should improve experimental study design, in turn increasing the efficiency of biomarker development and facilitating the delivery and deployment of novel clinical tests.1

Biomarkers can be measured in just about any body fluid available. Traditionally blood is the matrix of choice. However due to potential impediments such as the Blood Brain Barrier (BBB) and certain cells, membranes or systems such as the lymphatics, certain analytes may not be present in the fluids that make up these systems. However, as detection limits improve day to day, analytes that were thought not be present in certain fluids are now in fact being found. Saliva is indeed one of these fluids and is growing in popularity as a potential non-invasive, real time matrix.

As noted above, changes in individual or a group of genes results in 'bad signals' being created. The effect, 'abnormal' or indeed new proteins are formed which may be indicative of a particular disease or condition. For example Prostate Specific Antigen (PSA) as seen in prostate hypertrophy and/or cancer.

The issue then becomes, is this protein biomarker both sensitive (will changes be seen dependent on level of disease or during the treatment process), and specificity (is the biomarker specific only for that disease or can it be seen in other diseases/conditions).

All in all, medicine is slowly pushing away from a 'one size fits all' type of approach and looking to validate the use of several biomarkers to maximise specificity in particular.

Non biological fluid type measures such as Transcranial Magnetic Stimulation (TMS) as used in TBI analysis for example are also been thrown into the mix to help strengthen validity and ultimately diagnosis.

'The True Path'

The 'golden egg' in the quest to understand and define TBI is not the diagnosis of the pathology, but more so the 'quantification', individualisation and an definitive tool to assist with return to play, school, work and duty decision making. 

The much lauded protein markers do not hold this potential. Not even as true diagnostics (as highlighted in the figure at above.(click to view)). miRNA hold real potential in the diagnostic space and true potential as a monitor of drug response (as specific TBI drugs are invented and trialled). 

The ultimate biomarker will be that which corresponds directly with DNA outcome post injury which of course correlates directly to the pathology. This may be some years away but the logical step now is to firmly grasp and use our understanding of small RNA based analysis and move away from protein biomarkers (or at least use in combination), to accelerate beneficial outcomes for those about to or already suffering from TBI related conditions.

1, Nader Rifai, et al. Nature Biotechnology 24, 971 - 983 (2006)