Emerging therapeutic strategies based on the mechanism and pathogenesis of CNS disorders

Despite the fact that the central nervous system (CNS) disease treatment market accounts for nearly 20% of the overall therapeutics market and has significant unmet medical needs, the recent development and approval of antibody therapies such as Lecanemab have not been matched by similar breakthroughs for various CNS disorders, including depression, schizophrenia, sleep disorders, anxiety-related disorders, ADHD, autism, epilepsy, and stroke. The successful development of ketamine, which functions differently from the traditional neurotransmitter transport inhibitors typically targeted in depression treatment, along with the recent approval by the U.S. FDA of xanomeline-trospium—a novel medication targeting the M1 and M4 receptors—marks a significant shift in the treatment paradigm for schizophrenia, moving away from conventional D2 blockers. This is particularly noteworthy given the decade-long absence of new approvals for the disorder. These advancements highlight the potential for discovering new treatment targets and developing novel therapies through a better understanding of the underlying mechanisms and causes of CNS disorders. In this Collection, we aim to present the latest research findings and review papers focused on innovative therapeutic strategies and candidate identification based on the mechanisms of disease pathogenesis and brain function abnormalities in refractory brain disorders, which include neurodevelopmental, neuropsychiatric, and neurological disorders.