CNS Target Identification and Validation: Avoiding the Valley of Death or Naive Optimism?

Area of Science:

• Neuroscience
• Pharmacology
• Drug Discovery

Background:

• Central nervous system (CNS) disorders represent a major unmet medical need with substantial societal and healthcare costs.
• Despite this need, the past two decades have seen limited success in CNS drug approvals, causing many pharmaceutical companies to reduce investment in this area.
• The high failure rate in CNS drug discovery is likely due to multiple factors.

Purpose of the Study:

• To review existing methodologies for identifying and validating novel molecular targets for CNS drug discovery.
• To propose innovative strategies aimed at enhancing the success probability of developing new CNS therapeutics.
• To address the multifactorial reasons behind past failures in CNS drug development.

Main Methods:

• Literature review of historical CNS drug discovery approaches.
• Analysis of factors contributing to the low success rate of CNS drug approvals.
• Discussion of potential new strategies for target identification and validation in CNS disorders.

Main Results:

• Previous methods for target identification and validation in CNS drug discovery have had limited success.
• The selection of biologically plausible and disorder-relevant molecular targets is crucial for improving drug development outcomes.
• A critical evaluation of past failures is necessary to inform future strategies.

Conclusions:

• Improving the success rate of CNS drug discovery requires a re-evaluation of target selection and validation processes.
• Novel strategies are needed to overcome the challenges inherent in developing treatments for CNS disorders.
• A more robust approach to identifying and validating CNS targets could lead to more effective therapies for these debilitating conditions.