Neurological Biomarkers in Efficacy Studies Now Available

Jun 13 2013

In compound efficacy studies, potential drug candidates are evaluated for their true effect on molecular targets and general disease progression. Performing in vivo assessments of the compound on behavioral (phenotypic, sensory-motor function and cognition) and imaging endpoints gives valuable information on general efficacy, but may leave open questions at the cellular level within the brain. Each neurological disease has specific hallmarks that can be replicated in animal models (e.g., amyloid plaques, Tau phosphorylation and markers of neuronal cell death) that together lead to the cognitive deficits seen in Alzheimer’s disease and the CVN mouse, respectively. These endophenotypic hallmarks are considered biomarkers that can be followed up longitudinally and evaluated by several methods.

We can now analyze immunohistochemical biomarkers using a confocal microscope. By having multiple images taken at relatively high magnification, we are able to construct an image of the brain section in good resolution. This kind of analysis method provides valuable information on the expression of the protein of interest within the region of interest. However, when more accurate information on the number of immunoreactive cells within the region of interest is needed, unbiased stereological analysis is the gold standard for these type of studies. Combining these two methodologies provides our scientists with a good set of tools to study the compound efficacy in more general, high-throughput way and also enables fine details in the region of interest to be chosen based on the preliminary screening.

Biomarkers like those mentioned above support the findings from in vivo efficacy studies involving behavioral and imaging analysis and they give more in-depth information about the molecular and cellular targets that are being aimed at in various disease models. Biomarkers also aid in piecing together the translational aspects that may exist between the actual human disease and the animal model of the disease being employed, and thus add an overall value to drug discovery in neurological diseases like Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke and traumatic brain injury (TBI).

To learn more about how our biomarker testing and study services can support your drug discovery research, please contact us at askcharlesriver@crl.com.