Diana Mihaela Cofaru 1 *, Raluca Miruna Lupu 1, 2, Lorena Dima 1
1 Department of Fundamental, Prophylactic and Clinical Disciplines, Faculty of Medicine, Transilvania University of Brașov, Brașov, Romania
2 Clinical Neurology Department I, Clinical Hospital of Psychiatry and Neurology Brașov, Brașov, Romania
* Correspondence to: Diana Mihaela Cofaru, Department of Fundamental, Prophylactic and Clinical Disciplines, Faculty of Medicine, Transilvania University of Brașov, Brașov, Romania. E-mail: dianacofaru13@gmail.com
Abstract
Multiple sclerosis is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system for which therapeutic options have expanded considerably over recent decades. Although current disease-modifying therapies effectively suppress relapses and focal inflammatory activity in many patients, disability may continue to accumulate through progression independent of relapse activity (PIRA), highlighting the contribution of persistent compartmentalized CNS inflammation, axonal injury, and insufficient repair mechanisms that remain incompletely addressed. This narrative review aims to present and analyze the main therapeutic strategies targeting mechanisms involved in multiple sclerosis progression. For each of these directions, the available clinical results are discussed, together with the main limitations that currently prevent their widespread implementation in clinical practice. The studies reviewed indicate that several promising strategies may target disease mechanisms that are insufficiently influenced by current treatments. However, favorable effects on biological or imaging markers have not consistently translated into meaningful reductions in disability progression, highlighting the gap between measurable biological effects and clinical efficacy. Future treatment strategies may therefore require an integrated, mechanism-based approach combining control of peripheral and compartmentalized CNS inflammation with strategies aimed at limiting axonal injury and promoting remyelination and repair, supported by biomarker-guided patient selection.