ICORD + TGen: Evaluating SCI in a new way

Seth (L) and Femke (R)

Seth (L) and Femke (R)

The current, widely used classification tool for spinal cord injury is the ASIA (American Spinal Injury Association) Impairment Scale (AIS). The AIS is based on the patient’s neurological response, sensitivity to a light touch or pin prick in specific areas of the skin, and the strength of certain key muscle groups. The underlying basis behind this scale is that a particular level of the spinal cord and its corresponding spinal nerve supplies specific regions of the body. Any movement or sensation in a particular region lets the clinician know that its respective nerve is functioning and helps to determine the extent and severity of the patient’s spinal cord injury (SCI).

While the scale is widely used, it has been argued that an AIS assignment may not always provide an accurate prognosis due to confounding factors that limit examination. For example, the body areas demarcated for specific spinal nerves can differ between individuals and thus reduces the consistency of this scale. In addition, patients who have just suffered an SCI may not be fully conscious or may be under the influence of drugs or alcohol, lowering the scale’s accuracy due to this subjectivity. One of the goals of Dr. Brian Kwon and his research team is to develop an objective tool to evaluate injury severity and predict neurological outcome in patients who suffered an SCI, so that they can be treated post-injury as optimally and efficiently as possible.

In 2010, Dr. Kwon and his research team published a paper describing how the expression level of various proteins in the cerebrospinal fluid (CSF) that circulates in the space surrounding the spinal cord can better predict motor outcome 6 months after sustaining an injury compared to the standard AIS classification. Some of these proteins were also detectable in the peripheral blood, albeit at a very low concentration.

There is no doubt that blood samples are easier to collect than CSF; however, the development of reliable and stable blood biomarkers of SCI have been extremely difficult to identify. Interestingly, recent studies have reported significant levels of various small RNA molecules, scalled microRNAs (miRNAs), in serum and other bodily fluids following Alzheimer’s disease, traumatic brain injury and stroke. This raises the possibility that circulating miRNAs could serve as useful clinical biomarkers for SCI.

Seth Tigchelaar is a PhD student in Dr. Kwon’s laboratory at ICORD. His research is focused on determining if traumatic SCI of varying injury severity provide unique miRNA fingerprints, particularly useful for the classification of SCI. In order to detect and quantify SCI specific miRNAs in blood and CSF samples, Seth will be using state-of-the-art sequencing technology, a relatively new technique used to profile thousands of transcripts simultaneously during a single experiment.

During the 2013 Society for Neuroscience (SFN) conference in San Diego, Seth had the opportunity to meet Dr. Kendall Van Keuren-Jensen of the TGen neurogenomics group, whose laboratory is focused on neurodegenerative diseases, particularly Amyotrophic Lateral Sclerosis, Alzheimer’s disease and Parkinson’s disease. They were among the first to apply next-generation sequencing to profile the miRNA fraction of human CSF. Together with Dr. Brian Kwon and Dr. Femke Streijger, Seth travelled to Phoenix, Arizona to visit the team at the Translational Genomics Research Institute (TGen), a genomics laboratory with affiliations to Arizona State University and the University of Arizona.

Over the span of two warm weeks in Arizona and with the expertise and guidance of Dr. Kendall Van Keuren-Jensen and her team, Seth mastered the protocol and techniques needed to isolate and sequence miRNA. “It was a very exciting process, to learn from the experts in this field, and be able to perform Next-Gen sequencing, myself,” said Seth. Presently, Seth is working with Dr. Corey Nislow at UBC Pharmaceutical Sciences where some of the next-gen sequencing technology exists, and is awaiting the results of the sequence data on the miRNA profile from blood and CSF samples taken from human SCI patients that he analyzed in Arizona.