INCF Workshop on Genetic Disease Models of Psychiatric and Neurological Diseases

Abstract

This workshop was organized by the INCF Secretariat in collaboration with Martien Kas, Magali Haas and Rob Williams. It was held on February 14 - 16, 2013, in Utrecht, The Netherlands. Developing treatments for human diseases requires knowledge of the biological mechanisms underlying the disease states. This can only be gained through functional studies in which the course of disease is manipulated systematically using pharmacologic, environmental, and genetic interference. Experimental model systems are critical for resolving these scientific challenges, and researchers often select mice as the animal model. Brain disorders have a major societal and economic impact, but understanding these disease states is complicated because their underlying etiologies are not well characterized. This lack of knowledge about the mechanisms of brain disease has severely impeded the development and implementation of effective treatments using translational research approaches. Furthermore, brain disorders are complex and all factors, from genetic variation to disease development to environmental and behavioral influences, must be fully characterized to develop novel therapeutics. In 2009, the INCF held the 1 st INCF Workshop on Genetic Animal Models for Brain Diseases to address the potential role of Neuroinformatics in the development, evaluation, and use of genetic animal models for brain diseases. A key finding from this workshop was the increased need for standardized and interoperable database resources in which different modality phenotype data from available disease models and wild type animals can be integrated. To further explore the findings of the 1st INCF Workshop on Genetic Animal Models for Brain Diseases, INCF in association with One Mind for Research convened a second workshop that focused on genetic disease models of psychiatric and neurological diseases which was held in Utrecht, Netherlands on February 14-16, 2013. The workshop was organized around three disease states: traumatic brain injury (TBI), autism spectrum disorder (ASD), and Alzheimer’s disease (AD). For each disease state, the core disease phenotypes were clinically defined and available data from current animal models were evaluated. This information was then aligned with the genetic background based on animal models and the specific human genetic architecture. Next, the workshop examined the degree of agreement between basic science research and clinical outcome measures along with the impact this has on drug evaluation. The program concluded with efforts to bridge the translational gap between preclinical models and clinical trials, such as has been done with the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. Overall, the goals of the workshop were to: 1. Determine the criteria for core symptom definitions of brain diseases 2. Make recommendations for studying these core symptoms in mice based on current needs, limitations, and opportunities 3. Determine at what level human disease genetic architecture is critical for mouse models of brain diseases 4. Determine to what extent mouse and studies for brain diseases should be optimally aligned (e.g., in view of drug development)