Cognition Models and Drug Discovery

Excerpt

Cognitive impairment is common in a variety of neurological and psychiatric conditions, including stroke, Alzheimer’s disease (AD), Parkinson’s disease, traumatic brain injury, and schizophrenia. Currently available medications are relatively ineffective in treating cognitive dysfunction. Thus, cognitive dysfunction represents an important unmet medical need, and developing treatments is a major area of research interest in the pharmaceutical industry.

Identification of potential pharmacological treatments for cognitive disorders is highly dependent on the availability of adequate animal models [1]. Animal models of cognitive function are used in the identification and validation of molecular targets and serve as screening tools to identify and evaluate specific compounds for their potential efficacy. Ideally, animal models of cognition could provide a prediction of the specific conditions for which compounds would be most useful and could be combined with toxicology and safety pharmacology models to estimate the therapeutic index. Given the duration and expense of clinical trials, particularly for progressive degenerative conditions such as Alzheimer’s disease, it is becoming more important in drug discovery to maximize the potential for success through the development of high-quality animal models and their judicious use in selecting compounds for advancement into human studies.

The term “cognition model” requires some clarification. The term is frequently applied to the means by which cognitive processes are assessed in animals. Thus, the radial arm maze and the Morris water maze are often described as cognition models. However, perhaps a more precise use of the term “cognition model” would apply it exclusively to such measurements made in the context of some disease-relevant impairment of performance. Here, the term would not be applied to the radial maze or the water maze itself, but rather to the use of these tools in animals impaired, for example, by overexpression of β-amyloid in an attempt to mimic aspects of Alzheimer’s disease. To avoid confusion, the use of the term “model” in this chapter is restricted to the latter case, and the terms “assay” or “measure” are used to describe the tasks and procedures used to assess cognitive function.