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World J Clin Cases. Oct 26, 2024; 12(30): 6361-6373
Published online Oct 26, 2024. doi: 10.12998/wjcc.v12.i30.6361
Overview of emerging therapies for demyelinating diseases
Robert Medina, Ann-Marie Derias, Maria Lakdawala, Skye Speakman, Brandon Lucke-Wold
Robert Medina, Ann-Marie Derias, Maria Lakdawala, Skye Speakman, University of Florida College of Medicine, University of Florida, Gainesville, Fl 32610, United States
Brandon Lucke-Wold, Department of Neurosurgery, University of Florida, Gainesville, FL 32611, United States
Co-first authors: Robert Medina and Ann-Marie Derias.
Co-corresponding authors: Robert Medina and Brandon Lucke-Wold.
Author contributions: Medina R wrote the abstract, introduction, and background information sections (mechanism of remyelination, current models of inducing remyelination to reverse disease course, cellular mediators of remyelination, and inflammation and remyelination), created tables, and assisted with formatting and references. Derias A wrote the current advancements in the treatment of multiple sclerosis (remyelination of MS, infusion therapy, inhibition techniques, immune reconstruction therapies) and current advancements in the treatment of other diseases sections (optic neuritis, MOGAD, and ADEM), created figures, and assisted with formatting and references. Lakdawala M wrote the mechanisms of emerging therapies section (OPC differentiation, mesenchymal stem cells, molecular mediators of myelin repair) and current advancements in the treatment of other diseases sections (NMSOD, transverse myelitis, and peripheral nerve injuries), and created figures. Speakman S.M. wrote the background information section (failure of remyelination), created tables, and proofread/edited the final manuscript. All authors wrote the conclusion, created associated citations, assisted with editing all sections, and have read and approved the final manuscript.
Conflict-of-interest statement: All authors report no conflicts-of-interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Robert Medina, University of Florida College of Medicine, University of Florida, 1600 SE Archer Road, Gainesville, Fl 32610, United States. medina.robert@ufl.edu
Received: April 22, 2024
Revised: August 18, 2024
Accepted: August 21, 2024
Published online: October 26, 2024
Processing time: 134 Days and 15.6 Hours
Abstract

This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types–oligodendrocyte precursor cells (OPCs), astrocytes, and microglia–and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients’ quality of life.

Keywords: Central nervous system disease; Autoimmune; Remyelination; Demyelination; Myelin; Oligodendrocyte; Emerging therapies; Multiple Sclerosis

Core Tip: Autoimmune disorders of the nervous system still pose a significant therapeutic challenge. Current treatments focus on symptom management but no cure exists. Since many of these disorders are caused by demyelination, it follows that remyelination may be key in finding a cure. Promising new research focuses on the use of endogenous cellular and inflammatory mediators to induce remyelination in patients with demyelinating diseases. These efforts may culminate in treatments such as stem cell transplantation and signaling pathway manipulation. In addition to these systemic therapies, nerve guide conduits have shown promise in aiding the recovery of peripheral nerve injuries.