Chapter 8.1: Imaging as a CNS Biomarker

The discovery of novel safe and effective medicines for the treatment of many CNS disorders remains uniquely challenging due to their slowly progressive yet ill-defined pathophysiology, the subjective nature of the clinical assessment of signs and symptoms of disease and the relative inaccessibility of the brain to biological investigation. Clinical trials consequently require the study of large numbers of subjects, but still fail frequently because of the lack of objective markers for drug target engagement and functional pharmacodynamics that can be used to guide clinical dose and patient selection, to increase the likelihood of detecting robust efficacy signals. Recent advances in brain imaging provide opportunities to develop biomarkers for diseases of the central nervous system (CNS) that provide objective evaluations of disease state and drug effects. This review provides an overview of the potential for neuroimaging to provide readouts of brain function, structure and chemistry that could be used as biomarkers to facilitate decision making during the development of therapies for CNS disease, or that can be used clinically to guide diagnosis and treatment. The scientific validation, clinical qualification and regulatory acceptance of imaging biomarkers for CNS disease will help speed up the identification, development and registration of new therapeutics targeted to patients most likely to benefit from them.