Multiple Sclerosis: Practical Comprehensive Essentials

By Mike K.S. Chan and Dina Tulina

Multiple sclerosis (MS) is a progressive neurological disease that affects millions of people worldwide. Currently, the causes of MS are still unclear and the cure remains symptomatic, while the effectiveness of treatment varies widely among individuals. The clinical features and neurological defects derived from this progressive neurological disease are diverse since MS may affect the human central nervous system (CNS)) at all levels from the brain to the end of the spinal cord. Immunopathogenesis of MS involves many steps, including activation of peripheral leucocytes against putative CNS antigens, activated leucocytes with inflamed cerebral endothelial cells, the migration of activated lymphocytes and macrophages through the endothelium to the CNS environment, and further propagation of a massive immune response within the CNS. Such large-scale immune activation leads to loss of the myelin-oligodendrocyte complex. Various types of immune cells and mediators of the immune-inflammatory response actively contribute to MS pathogenesis. Genetic factors are also thought to play a central role in the development of most forms of MS. Axonal degeneration and neuronal loss are the core components of irreversible and permanent CNS atrophy and disability in MS.

This book provides a comprehensive overview of the current MS situation as researchers try to understand the process and develop treatments that can slow or stop the disease, possibly repair the damage, alleviate specified symptoms, and improve the abilities of MS patients to function in everyday life. Various biological holistic approaches have been shown to slow disease progression in some patients, and the recovery rate of cellular mechanisms in the brain and spinal cord has been accelerated, increasing the possibility of achieving complete balance of the disease state.

The panel reviews the background, focusing on novel strategies that are most likely to understand the biological mechanisms of recovery and translate findings into alternative comprehensive approach to the MS management. The modality of such complementary therapies adds a new dimension, geared to further improvement in the management and sustain the acquired long-term results of MS. This book will be necessary to researchers, research funders, healthcare advocates of MS research and treatment, and interested patients and their families.

• Language: English
• Publisher: Troubador Publishing Ltd
• Release date: Jun 28, 2022
• ISBN: 9781803133454

Mike K.S. Chan

Prof. Dr. Mike K.S. Chan is a Senior Researcher, Educator and author of multiple books on Biological, Integrative and Regenerative Medicine, including stem cells, with over three decades of experience in all of the fields. He is an Associate Professor of American Academy of Stem Cell Physicians (AASCP) and Board Member/Head of Regenerative Medicine of several world-renowned organisations including European Society of Preventive, Regenerative and Anti-Aging Medicine (ESAAM).

Book preview

Multiple Sclerosis

Practical Comprehensive Essentials

Main authors:

Professor Mike K. S. Chan, PhD, Postdoc (Regenerative Medicine)

Dr Dina Tulina, MD, MSc, Postdoc (Psychiatry)

Contributors to Subsection ‘Targeted Neural

Precursor Stem Cells: Mechanism of Function’

Dr Shing Yi Pan, BSc (Biomedical Science), PhD

Yee Hui Rong, BSc (Biomedical Science)

Yenny Kenisi, BSc (Biomedical Science)

Editor

Dr Dina Tulina, MD, MSc, Postdoc (Psychiatry)

Copyright © 2022 Mike K.S. Chan and Dina Tulina

The moral right of the author has been asserted.

Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers.

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TABLE OF CONTENTS

FOREWORD

ABBREVIATIONS

INTRODUCTION AND DISEASE PATHOGENESIS

PART I

Pathology And Diagnosis

1.1 Aetiology

1.2 Epidemiology and Genetics

1.3 Pathophysiology

1.4 Classification

1.5 The Course of MS

1.6 Clinical Features

1.7 Cognitive Impairment in MS

1.8 Diagnosis and Magnetic Resonance Imaging

PART II

Management

2.1 Treatment and Prevention

Immune-Modulating Peptides (Transfer Factor™)

Active Specific Immunotherapy (ASI) Therapy

Neural Mito Organelles (MO) Peptides

2.2 Mechanisms and Potentials of Stem Cells

Advantages and Drawbacks of Various Types of Cells

Targeted Neural Precursor Stem Cells: Mechanism of Function

CNS Remyelination Mechanisms

Mesenchymal Precursor Stem Cells: Mechanisms of Function

Embryonic Stem Cells (ESC) and Induced Pluripotent Stem Cells (iPSC)

2.3 Diet Facts and Management

Fatty Acids as a Risk Factor in MS Development

Salt in Typical ‘Western Food’

2.4 Physiotherapy in Treatment and Symptom Management

Hyperbaric Oxygenation Therapy (HBOT)

Morphogenetic Harmoniser System: the Scalar Plasma Wave Modulator

Transcranial Direct Current Stimulation (tDCS)

Transcranial Magnetic Stimulation (TMS)

2.5 The Role of Memory Training Centres

2.6 The Management of Spasticity

REFERENCES

FOREWORD

Multiple sclerosis (MS) is a debilitating and disabling disease, mainly diagnosed in middle age, the course of which completely determines the future life of the individual. Most patients suffer from a permanent loss of ability to work and a deterioration in their quality of life. This determines the high social and economic significance of this disease.

There are many books on multiple sclerosis, ranging from patients’ own experiences to a detailed breakdown of the pathophysiological processes and the ways of influencing them. Many specialists and patients confronted with MS have become disillusioned with the therapies currently available. This occurs because there is no cure at present or even a sufficiently effective therapy for MS, and existing medicines can only alleviate symptoms and slow down the progression of the disease or reduce the number of relapses. In addition, the drugs are administered by injection throughout the life. Basic therapy consists of high-dose steroids (administered intravenously or orally) and is used to treat relapses, while damaging other organs as a result of side effects. Despite the severe diagnosis and the lack of a complete cure, there is a high probability of reversing the course of the disease, with the potential to continue enjoying a full life and complete physical and mental health.

This book introduces biological holistic approaches to the management of multiple sclerosis and the possibility of achieving a complete balancing of the disease state. The first part introduces the reader to a theoretical background and clinical features of the disease. The second part covers the mechanisms of treatment and prevention, and the basics of biomolecular and biological medicine and its potential. Consistent with recent discoveries in research and the likelihood of the gut and its microbiota to affect the development of disease, diet and its effect through the gut on the nervous and immune systems are also addressed in the next chapter. The importance of physiotherapy, medical rehabilitation and management of spasticity is paramount in the middle and late course of the disease, and this is covered in detail at the end of the book.

A book on the potential and biological approaches to managing multiple sclerosis was written with inspiration from the positive and long-term results obtained by clinicians using these technologies around the world. Let’s start the journey of new opportunities.

Professor Mike K. S. Chan and Dr Dina Tulina

ABBREVIATIONS

AhR – Aryl hydrocarbon receptor

ALS – Amyotrophic lateral sclerosis

APC – Antigen-presenting cell

ASI – Active specific immunotherapy

ATRA – All-trans retinoic acid

Ax – Axon

BBB – Blood-brain barrier

BCG – Bacillus Calmette-Guérin

BDNF – Brain-derived neurotrophic factor

Breg – Regulatory B cells

CIS – Clinically isolated syndrome

CNS – Central nervous system

CNTF – Ciliary neurotrophic factor

CSF – Cerebrospinal fluid

CFU-Fs – Colony-forming unit-fibroblasts

DC – Dendritic cell

DG – Dentate gyrus

DNA – Deoxyribonucleic acid

EAE – Experimental autoimmune encephalomyelitis

EDSS – Expanded Disability Status Scale

EEG – Electroencephalogram

ENT – Ear, nose and throat

GCL – Granule cell layer

GPRs – G-protein-coupled receptors

GWAS – Genome-wide association studies

HBOT – Hyperbaric oxygenation therapy

HDACs – Histone deacetylases

HLA – Human leukocyte antigen

IgA – Immunoglobulin A

IL-10 – Interleukin 10

iPSC – Induced pluripotent stem cell

iTBS – Intermittent theta bursts

LIF – Leukaemia inhibition factor

LCFA – Long-chain fatty acids

MCFA – Medium-chain fatty acids

ML – Molecular layer

MO – Mito organelles

MRI – Magnetic resonance imaging

MS – Multiple sclerosis

MSCs – Mesenchymal stem cells

MSFC – Multiple Sclerosis Functional Composite

mtDNA – Mitochondrial DNA

NaCl – Sodium chloride

NGF – Nerve growth factor

NK – Natural killer cells

NPCs – Neural precursor cells

Nrg1 – Neuregulin

NSCs – Neural stem cells

OPCs – Oligodendrocyte progenitor cells

P0 – Protein zero

PMP22 – Peripheral membrane protein of 22kDa

PNS – Peripheral nervous system

PPMS – Primary progressive multiple sclerosis

PSCs – Precursor stem cells

PUFAs – Polyunsaturated fatty acids

RA – Retinoic acid

RIS – Radiologically isolated syndrome

RNS – Reactive nitrogen species

ROS – Reactive oxygen species

RRMS – Relapsing-remitting multiple sclerosis

rTMS – Rhythmic transcranial magnetic stimulation

SCFA – Short-chain fatty acids

SPMS – Secondary progressive multiple sclerosis

SVZ – Subventricular zone

TBS – Theta-burst stimulation

Teff – Effector T cells

tDCS – Transcranial direct current stimulation

TMS – Transcranial magnetic stimulation

TNF – Tumour necrosis factor

Tregs – Regulatory T cells

Tr-1 Cell – Type 1 regulatory T cell

INTRODUCTION AND DISEASE PATHOGENESIS

Multiple sclerosis (MS) is heterogeneous, multifactorial, autoimmune, chronic inflammatory demyelinating¹ central nervous system (CNS) disease. More than 2.3 million people worldwide are living with MS,² a debilitating condition triggered by an autoimmune response that causes inflammation damage to nerve cells in the CNS.

The pathogenesis of MS is not well known, and there is a multitude of factors that may cause the onset of this disease. Genetic factors may play a major role,³ whereas other studies have indicated a correlation between pathogenic infections and the development of the disease.⁴ A lot of genetic variations are shared within different autoimmune diseases, suggesting several common pathogeneses.⁵ Currently, the most widely accepted hypothesis of MS is an autoimmune disease that affects genetically predisposed individuals afflicted with an environmental pathogen.⁶ Research results of the past decades indicate that the aetiology of most autoimmune diseases includes environmental features that overlap the genetically efficient profiles.⁷, ⁸

MS is a highly heterogeneous disease with very diverse pathological and clinical manifestations. Early stages present and are characterised by predominantly perivascular inflammatory infiltrates, usually in the brain, optic nerve and spinal cord, and consist of lymphocytes (CD4+ and CD8+ T and B cells), monocytes, and macrophages and eventually lead to plaque formation.⁹ The end stage is differentiated by demyelination, astrogliosis, and neuronal as well as axonal degeneration.¹⁰, ¹¹ It has been confirmed that dendritic cells, presenting antigen and activated autoreactive T cells, play a decisive role in the invasion of the CNS and in the whole process.¹², ¹³ In addition, innate and adaptive immune cells, such as CD8+ T cells, directly damage axons by secreting granzyme B and perforin, and macrophages damage the CNS by producing toxic molecules such as nitric oxide, oxygen radicals and pro-inflammatory cytokines.¹⁴

Fig.1. Effector T Cells in Multiple Sclerosis. Source: Baecher-Allan, et al. (2018).¹⁹ Description:

Peripherally activated T cells cross the blood–brain barrier (BBB) into the central nervous system (CNS), where they are reactivated and secrete cytokines to exert their effector functions. T helper (Th)-1 cells produce their lineage-defining cytokine IFNg, as well as TNFa, while Th17 cells secrete their defining cytokine IL-17, as well as IL-21 and IL-22, and can also express IFNg, which contributes to their pathogenicity. CD8+ effector T cells (Teffs) can also be a source of IL-17 and IFNg. This cytokine secretion leads to the activation of CNS-resident immune cells such as microglia, astrocytes and macrophages, as well as to the production of cytokines, increased antigen-presenting cell (APC) function, and the enhanced production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). CD8 T cells can also release cytolytic granules, causing axonal dissection. Effector T cells can be regulated in the periphery or in the CNS by FoxP3+ regulatory T cells (Tregs), and by Tr1 cells, CD8 Tregs, natural killer (NK) cells, and regulatory B (Breg) cells.

MS is determined as a chronic inflammatory disease of the brain and spinal cord with focal lymphocytic infiltration, which eventually harms myelin and axons.¹⁵ Primarily, inflammation is temporal, and remyelination happens but is not permanent, and as such, the early stages of MS are presented by incidences of neurological dysfunction followed by recovery.¹⁶ After some time, pathological changes become unavoidable and permanent due to proliferative microglial activation associated with extensive and chronic neurodegeneration, which clinically manifests as a progressive increase in disability.¹⁷

Until recently, it was believed that the violation of the conductive function