Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis.

Paweł Grieb,Agnieszka Kamińska,Konrad Rejdak,Maciej Świątkiewicz,Robert Rejdak,Anselm Jünemann

doi:10.3390/ph14040326

Abstract

In remitting–relapsing multiple sclerosis (RR-MS), relapses are driven by autoreactive immune cells that enter the brain and spinal cord and damage myelin sheaths of axons in white and grey matter, whereas during remissions myelin is repaired by activated oligodendroglial cells. Disease-modifying therapies (DMTs) may either retard/attenuate myelin damage or promote/enhance/speed up myelin repair. Almost all currently approved DMTs inhibit myelin damage and are considerably toxic. Enhancement of myelin repair is considered an unmet medical need of MS patients. Citicoline, known for many years as a nootropic and neuroprotective drug and recently pronounced food supplement, has been found to be significantly efficacious in two complementary rodent models of MS, experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced myelin toxicity. Moreover, citicoline treatment improves visual evoked potentials (VEPs) in glaucoma patients, which is relevant because VEP monitoring is frequently used as an indicator of remyelination in MS. Although over-the-counter availability of citicoline may impede its formal translation to the clinic of MS, evaluation of its efficacy for supporting remyelination in this disease is strongly indicated.

Highlights

Accepted: 29 March 2021Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS), affecting between 2 and 2.5 million people throughout the world, mostly in the Northern Hemisphere [1]
The disease is described as a brain- and spinal cord-specific chronic immunoaggressive process that affects the CNS, initially damaging myelin sheaths of axons [3]
In RR-March 2021Multiple sclerosis (MS), relapses are caused by immune cells invading CNS and damaging myelin, while remissions involve activation of oligodendroglia and oligodendroglial precursors, and remyelination, which protects axons from degeneration (Figure 2) [10]

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS), affecting between 2 and 2.5 million people throughout the world, mostly in the Northern Hemisphere [1]. In the transition period from RR-MS to SP-MS, relapses and remissions become less and less frequent, but neurological disability outside relapses continuously accumulates [4] It is not clear whether RR-MS and SP-MS are two forms of the same disease or whether they represent distinct pathologies. In the essaybut we supporting will overview current effective in controlling the inflammatory of present the disease, myelin concepts concerning pathomechanisms and therapies of MS and justify the opinion that regeneration is still an unmet medical need [6]. CNS and damaging myelin, while remissions involve activation of oligodendroglia and oligodendroglial precursors, and remyelination, which protects axons from degeneration (Figure 2) [10]. In RR-MS, relapses are caused by immune cells invading CNS and damaging myelin, while remissions involve activation of oligodendroglia and oligodendroglial precursors, and remyelination, which protects axons from degeneration (Figure 2) [10]. The degree of demyelination may be an important pathological correlate of clinical progression

Preclinical Models of MS

Disease-Modifying Therapies for MS

Visual Evoked Potentials for Monitoring Remyelination

Pharmacodynamics of Citicoline

Assessment of Citicoline in Preclinical Models of MS