Complementary strategies to be used in conjunction with animal models for multiple sclerosis drug discovery: adapting preclinical validation of drug candidates to the need of remyelinating strategies.

Introduction: The quest for novel MS therapies focuses on promoting remyelination and neuroprotection, necessitating innovative drug design paradigms and robust preclinical validation methods to ensure efficient clinical translation. The complexity of new drugs action mechanisms is strengthening the need for solid biological validation attempting to address all possible pitfalls and biases precluding access to efficient and safe drugs.

Areas covered: In this review, the authors describe the different in vitro and in vivo models that should be used to create an integrated approach for preclinical validation of novel drugs, including the evaluation of the action mechanism. This encompasses 2D, 3D in vitro models and animal models presented in such a way to define the appropriate use in a global process of drug screening and hit validation.

Expert opinion: None of the current available tests allow the concomitant evaluation of anti-inflammatory, immune regulators or remyelinating agents with sufficient reliability. Consequently, the collaborative efforts of academia, industry, and regulatory agencies are essential for establishing standardized protocols, validating novel methodologies, and translating preclinical findings into clinically meaningful outcomes.