What makes a prognostic biomarker in CNS diseases: strategies for targeted biomarker discovery? Part 1: acute and monophasic diseases

Expert Opin Med Diagn. 2011 Jul;5(4):333-46. doi: 10.1517/17530059.2011.578624. Epub 2011 May 27.

Abstract

Introduction: Biomarker discovery studies are sometimes referred to as fishing exercises as the excitement of discovering a potentially important new biomarker is offset by the likelihood of finding something that is barely useful. For biomarkers to increase their prognostic value, biomarkers need to improve the current prognostic accuracy. In this regard, one potential advantage in biomarker discovery for acute neurological disease is that damage-related release of biomarkers can be timed, allowing for targeted sample collection.

Areas covered: In this article, the authors focus on the accuracy of prognosis for the following acute and monophasic neurological diseases: Guillain-Barré syndrome, stroke, traumatic brain injury and subarachnoid hemorrhage. For each condition, the prognostic accuracy, based on clinical information, is compared with the potential gain using biomarker data.

Expert opinion: Lessons have been learned from discovery studies on prognostic protein biomarkers in all of the diseases mentioned. The data provided allow the prognostic value of future biomarkers to be increased through the definition of criteria that future biomarkers must surpass. A class IV rating was given for the value of each biomarker. Two distinct but targeted strategies may be useful for future biomarker discovery in acute conditions: strategies focused on biomarker discovery from acutely damaged tissue (e.g., laser capture microdissection); and strategies focused at eloquent time points (e.g., based on selecting high-likelihood samples that are positive for already established biomarkers). Validation studies, both analytically and clinically, are a key requirement for the success of future biomarker discovery.