Novel Drugs in a Pipeline for Progressive Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a widely known inflammatory, demyelinating disease of the central nervous system. The pathogenesis of progressive multiple sclerosis (PMS) is a complex, multi-level process that causes therapeutic difficulties. Along with variables such as age and duration of the disease, pathogenetic mechanisms change from inflammatory to neurodegenerative processes. Therefore, the efficacy of available anti-inflammatory drugs approved for the treatment of PMS, such as ocrelizumab or siponimod, is limited in time. In search of innovative solutions, several research studies have been conducted to evaluate the effectiveness of drugs with neuroprotective or remyelinating effects in PMS, including biotin, ibudilast, simvastatin, alpha-lipoic acid, clemastine, amiloride, fluoxetine, riluzole, masitinib, opicinumab, and lamotrigine. The current review includes those compounds, which have entered the clinical phase of assessment, and the authors discuss future prospects for successful PMS treatment.

Comparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia–ischemia in newborn rats: a multi-drug randomized controlled screening trial

“…The neuroprotective effects are mainly due to its anti-inflammatory properties in addition to an improvement of myelination and oligodendrocyte differentiation 46 . Clemastine has lately become a promising treatment option for patients suffering multiple sclerosis 47 . In an experimental neonatal study of chronic hypoxic brain injury, Clemastine was shown to rescue myelination defects and to promote functional recovery 48 .…”

Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront

“…Presently, ocrelizumab, a monoclonal antibody, is the only approved treatment for PPMS [ 48 ], while siponimod, a small-molecule drug, is approved for SPMS [ 49 ]. As mentioned by Sapko et al [ 50 ], treating PMS is particularly challenging due to its complex pathogenesis, which shifts from primarily inflammatory to predominantly neurodegenerative processes with age and disease duration [ 50 , 51 ]. Consequently, the window for effective use of anti-inflammatory treatment is very narrow, emphasizing the need for neuroprotective and remyelinating therapies [ 50 ], although trials have shown inconclusive results so far [ 50 , 51 ].…”

Swept-Source Optical Coherence Tomography Thresholds in Differentiating Clinical Outcomes in a Real-World Cohort of Treatment-Naïve Multiple Sclerosis Patients

“…Predominant neuro-axonal loss in about 10-15% of patients leads to a gradual disability progression Brain Sci. 2023, 13, 591 2 of 13 from the disease onset, referred to as primary progressive MS (PPMS) [2,4,5]. A relatively mild disease course, called benign MS (BNMS), is observed in a subset of patients [6].…”

“…In most cases, RRMS characterized by pathogenic immune responses is followed by a phase of insidious disability accrual with underlying neurodegenerative processes, termed as secondary progressive MS (SPMS) [ 1 , 3 ]. Predominant neuro-axonal loss in about 10–15% of patients leads to a gradual disability progression from the disease onset, referred to as primary progressive MS (PPMS) [ 2 , 4 , 5 ]. A relatively mild disease course, called benign MS (BNMS), is observed in a subset of patients [ 6 ].…”