Medical Needs & Failures, Target Discovery
Full course description
Students will become acquainted with existing treatments, current and new targets in Neuroscience, i.e. how current knowledge of neuropsychiatric disease processes relates to existing medicinal drugs and research and development of new medicinal drugs. In this course we will focus on identifying neurobiological substrates of major Neuropsychiatric diseases such as Alzheimers Disease and Schizophrenia for which there still exist largely unmet medical needs, because of incomplete or absent treatment efficacy. This will be annotated with examples from the literature.
For example in Alzheimers Disease only symptomatic pharmacological treatments are available while to date there is extensive research and development of novel disease modifying biologics treatments. This is a therapeutic area where many clinical trials have failed in the recent past. Ongoing investigations focus on vaccine or antibody treatments aimed at clearance or prevention of amyloid plaques and neurofibrillary tangles in order to obtain primary prevention therapies. Some attention will also be paid to drug development for rare diseases, specifically Autism. How to investigate the neural substrates that may be treatable with drugs, is unravelled by the Research Diagnostic Criteria (RDoC) project. Potential applications for RDoC have recently expanded to treatment development and clinical trials, given its potential for circuit-based treatment targets as compared to trials using current categories that suffer from excessive heterogeneity and questionable validity.
Students will understand:
- the similarities and differences between biomarkers (e.g. in Alzheimers Disease: brain amyloid obtained by PET-scan), disease targets (amyloid volume in Alzheimers Disease), drug targets (amyloid in temporal lobe area) and clinical targets (memory performance);
- the principles and the levels of aggregation (from molecule to behavioural function) in the RDoC framework;
- the public/private collaboration in Autism Drug Development (EU-AIMS);
- human pharmacological models of psychotic symptoms as method for drug screening.
- R. Schreiber