Dihydroorotate Dehydrogenase Inhibitors as Emerging Therapeutic Targets in Multiple Sclerosis: Mechanistic Insights and Therapeutic Perspectives

SILPA VIJAYAN R

Dihydroorotate Dehydrogenase Inhibitors as Emerging Therapeutic Targets in Multiple Sclerosis: Mechanistic Insights and Therapeutic Perspectives

Author(s)	Ms. SILPA VIJAYAN R
Country	India
Abstract	Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disorder that is associatedwith neuroinflammation, demyelination, and progressive axonal damage within the central nervoussystem (CNS). There occurs a complex interplay between genetic susceptibility, environmentaltriggers, and immune dysregulation, leading to the activation of autoreactive lymphocytes that target myelin antigen components, which is the basic etiology behind the progression of the disease.There exist a number of limitations for the currently available disease-modifying therapies ofMultiple sclerosis, such as partial efficacy, adverse effects, and the inability to completely ceaseprogression of the disease. Recent advances in molecular immunology and the emerging evidence have demonstrated certain metabolic pathways as essential promising therapeutic targets involvedin immune cell proliferation. A mitochondrial enzyme, Dihydroorotate dehydrogenase (DHODH) isone of the critical advanced targets, which is responsible for the rate-limiting step in de novopyrimidine synthesis, and plays a crucial role in the proliferation of activated T and B lymphocytes. Restraining DHODH selectively suppresses actively dividing immune cells without significantlyaffecting resting immune cells, thereby contributing a targeted immunomodulatory approach. OralDisease-modifying drugs such as teriflunomide have already demonstrated clinical efficacy inrelapsing forms of MS, while next-generation DHODH inhibitors, including vidofludimus (IMU-838), are currently being explored for added benefits like selectivity, safety, and potency. This reviewdelineates the recent understandings of the epidemiology and pathophysiology of MS, underlinesthe molecular mechanisms responsible for immune-mediated neurodegeneration, and explore thepromising therapeutic significance of DHODH inhibitors. In addition to that, This review exploresnovel breakthroughs, potential biomarkers, and future investigational concepts for therapies thattargeting DHODH. Additionally, it discusses the role of DHODH inhibition in the development of next-generation treatment strategies for multiple sclerosis.
Keywords	Multiple Sclerosis, Dihydroorotate Dehydrogenase Inhibitors, De no pyrimidine synthesis
Field	Medical / Pharmacy
Published In	Volume 8, Issue 4, July-August 2026
Published On	2026-08-21

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Dihydroorotate Dehydrogenase Inhibitors as Emerging Therapeutic Targets in Multiple Sclerosis: Mechanistic Insights and Therapeutic Perspectives

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