Drug Discovery and Development in the Neurosciences

Launched March 2013 Updated August 2022 13 lectures

Discovery and development of new drugs in the neuroscience field have lagged behind other indication areas during the recent years. Neurologic disorders, psychiatric disorders, and pain are considered uniquely difficult and risky disease targets. Several biotechnology and pharmaceutical companies have downsized their neuroscience programs. Indeed, relative to other disease areas,... read moreneuroscience drug discovery and development suffer from limited understanding of disease mechanisms, few predictive animal models, few reliable translational biomarkers, and difficult, lengthy, and costly clinical trials. Furthermore, there are unique technical hurdles, such as the necessity to overcome the blood brain barrier for sufficient occupancy of the molecular target in the brain.

This currently dominant pessimistic view ignores recent successes as well as the heterogeneity of the neuroscience area. Seizure disorders and Multiple Sclerosis have seen remarkable progress with novel drugs reaching the patients. In both diseases, there have been significant advances in understanding of disease mechanisms. Animal models with strong predictive power have become available. Translational biomarkers and accepted proof-of-concept clinical trial designs have made it possible to establish efficacy of drugs in decisive trials. Alzheimer’s disease and Parkinson’s disease have seen breakthrough discoveries on the pathophysiology, which have identified strongly validated drug targets and associated biomarkers.

Parallel rapid advances in drug development brought several novel drug candidates to clinical trials. The pain field has obtained clinical efficacy for several new drug targets, but so far has been held back by unexpected safety issues. Psychiatric diseases, depression in particular, have seen least tangible progress, but groundbreaking discovery work on schizophrenia disease genes are beginning to draft possible disease mechanisms and associated drug targets.

The successes in seizure disorders and Multiple Sclerosis may serve as paradigmatic examples for other disorders in the neuroscience area. The progress in Alzheimer’s disease, Parkinson’s disease, schizophrenia, and pain illustrate the power of drug discovery approaches that are based on molecular understanding of the pathophysiology. Understanding disease mechanisms makes it possible to select drug targets with a high degree of validation and to identify related biomarkers that facilitate clinical development.