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Research Journal Feature: Biomarkers and Personalized Medicine

Personalized medicine is revolutionizing how we diagnose and treat illnesses these days. The diagnosis and treatment of disease can be tailored to each individual based on specific health information (sometimes genetic), resulting in better, more effective outcomes. In 2015, President Obama announced the Precision Medicine Initiative in his State of the Union address, which allocated $215 million to developing individualized care strategies. The National Cancer Institute received the largest chunk of money ($70M) to fund their efforts in cancer genomics. In clinical trials, studies that targeted cancer with personalized therapies resulted in an over 30% response rate, while the nonpersonalized treatments led to only 4.9% of participants responding. It is clear that the personalized therapies led to improved outcomes, even in people with cancers that were resistant to standard treatments.

You may be wondering what personalized medicine has to do with spinal cord injury (SCI). Since SCIs are usually the result of a traumatic event, it is impossible to do genetic testing to see who is at risk for getting one. And the presence of SCI is usually pretty easy to diagnose – loss of sensation and movement in the limbs is relatively clear in most cases. However, in the early stages (acute) it is often difficult to assess the severity of SCI, and the body’s natural inflammatory and immune responses can cause further damage. In addition, there is a lot of variability in spontaneous recovery after an SCI. Wouldn’t it be nice to have a tool to define the severity of an SCI within hours of onset, based on unbiased information that reflects the extent of the spinal cord damage? In the acute phase, neuroprotective strategies could then be targeted to the appropriate severity of injury. Later, rehabilitation could be personalized based on the predicted neurologic recovery.

Over the past few years, a team of researchers from The Miami Project and Department of Neurosurgery (Drs. Ross Bullock, Michael Wang, Helen Bramlett, Dalton Dietrich, Robert Keane, and Juan Pablo de Rivero Vaccari) have been looking for ways to assess and predict the outcome of acute spinal cord and brain injuries. In their studies, they obtain blood and spinal fluid samples acutely from newly-injured patients who were already undergoing spinal fluid drainage as a part of their clinical treatment. The scientists also looked at spinal cord tissue and fluid samples from rodent models of SCI and traumatic brain injury (TBI). They use  sophisticated methods and equipment to scan the samples for any biological indicators, usually proteins, which may be associated with injury to the central nervous system. The concentration levels of these “biomarkers” are measured and compared to samples from uninjured humans and rodents. They are then correlated to long-term neurologic status to see if they can predict injury severity. The researchers found numerous candidate biomarkers for SCI in both the human and rodent samples. While some proteins were found in higher concentrations (upregulated), others were found in lower concentrations (downregulated). The proteins that are highly specific to neural tissue could be used in the future as specific SCI biomarkers. This study is unique because several biomarkers were verified in both the human and rodent spinal fluid and/or spinal cord samples, which improves the potential for translation. In the future, the discovery and use of biomarkers for SCI and TBI could lead to development of new therapeutic interventions that can be applied to prevent or reduce disability.

Differential neuroproteomic and systems biology analysis of spinal cord injury. Moghieb A, Bramlett HM, Das JH, Yang Z, Selig T, Yost RA, Wang MS, Dietrich WD, Wang KK. Mol Cell Proteomics. 2016 May
5. pii: mcp.M116.058115. [Epub ahead of print]