Dr. Yusei Miyazaki is the chief neurologist and director of the multiple sclerosis/neuromyelitis optica spectrum disorder (MS/NMOSD) clinic at Hokkaido Medical Center (Sapporo, Japan). He graduated with an M.D. from Hokkaido University (Sapporo, Japan) in 1998. Following residency in internal medicine and neurology, he earned a Ph.D. in neuroimmunology in 2007 from Hokkaido University. Thereafter, he continued his post-doctoral research training at the National Center for Neurology and Psychiatry (Tokyo, Japan) and at McGill University (Montreal, Canada) as part of a Government of Canada Post-Doctoral Research Fellowship. As a physician-scientist, Dr. Miyazaki conducts basic and clinical research on MS/NMOSD and has more than 70 research publications in this field.

Abstract of Talk:

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) clinically characterized by recurrent attacks of neurological symptoms. Most patients have anti-aquaporin 4 autoantibodies in the circulation. Upon breakdown of the blood-brain barrier, these autoantibodies penetrate the CNS and trigger destructive inflammation. Progression of disability in NMOSD is dependent exclusively on the occurrence of attacks. With the exception of rituximab, treatments for preventing NMOSD relapse basically worked through nonspecific immunosuppression and had incomplete effectiveness as well as a broad spectrum of side effects. In 2019 and 2020, the effectiveness of four monoclonal antibodies—eculizumab, satralizumab, inebilizumab, and rituximab—was demonstrated one after the other in randomized controlled trials, and the results have led to the approval of these drugs in many countries. All these monoclonal antibodies have definite effectiveness in preventing NMOSD relapses with acceptable safety profiles. With the advent of these monoclonal antibody therapies, the treatment of NMOSD has entered a new era. In this lecture, I will share our experience treating NMOSD using these new monoclonal antibodies and discuss the best treatment strategy for NMOSD at present.

Dr Sudarshini Ramanathan is a neurologist and clinician-scientist, with subspecialty expertise in neuroimmunology. Dr Ramanathan is a staff specialist neurologist at Concord Hospital in Sydney. She completed her PhD and postdoctoral fellowship in neuroimmunology at the University of Sydney, and was a senior postdoctoral fellow at the University of Oxford working with the Oxford Autoimmune Neurology Group. She now leads a fundamental science and clinical research program and heads the Translational Neuroimmunology Group at the University of Sydney. Dr Ramanathan has received 14 continuous years of NHMRC fellowship funding, and is currently an NHMRC Investigator Fellow. She has authored over 60 publications in the field of autoimmune neurology. In 2013, Dr Ramanathan established and has since been the lead investigator of the Australasian MOGAD Study Group, which encompasses over 150 clinicians from 45 centres in Australia, New Zealand, and South East Asia. She leads the evaluation of a cohort of over 700 children and adults with myelin oligodendrocyte glycoprotein antibody-associated disease. Dr Ramanathan’s research program is focused on understanding the underlying immunobiology of autoimmune neurological disorders, in order to improve the diagnosis and treatment of patients who otherwise risk significant disability.

Abstract of Talk:

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is now recognised as a disease entity distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. This presentation will highlight the scientific and clinical evolution of our understanding of this condition, and the role of laboratory biomarkers and their strength and limitations in characterising this disorder. We will review the expanding clinical spectrum of MOGAD, and the clinical and radiological profiles which can distinguish this condition from other demyelinating syndromes and facilitate expedited diagnosis. This presentation will outline the development of the 2022 International MOGAD Diagnostic Criteria, and discuss therapeutic decision making both at disease onset and in the case of relapsing disease.

Dr. Wee Yong is a Professor at the University of Calgary. He leads the Multiple Sclerosis (MS) research program at the university and he directs the provincial Alberta MS Network. Dr. Yong has been the President of the International Society of Neuroimmunology, and he continues to co-direct its Americas and Global Schools of Neuroimmunology. Dr. Yong’s research interests lie in the area of neuroimmunology, neuroprotection and CNS regeneration, and his projects are guided by MS, glioblastoma and intracerebral hemorrhage. He has published 370 peer-reviewed manuscripts and his research has been translated into Phase 2 and 3 clinical trials in MS; his team has an ongoing Phase 1/2a trial in glioblastoma. His work has been cited over 36,000 times (h-index of 107) according to Google Scholar. Dr. Yong is an elected fellow of both the Canadian Academy of Health Sciences and the Royal Society of Canada. He received the 2017 Allyn Taylor International Prize in Medicine for ‘transformational discoveries in MS’. Dr. Yong was profiled in the August 2021 issue of the world’s #1 clinical neurology journal, Lancet Neurology.

Abstract

The slowly expanding lesion (SEL) detected by brain imaging grows gradually over years in the brain of people living with MS, particularly those with progressive MS. The number of SELs has been correlated with progression of disability. Analysis of postmortem MS samples highlights pro-inflammatory microglia at the rim of SELs, and several of these have iron deposition in their midst. Correspondent with these features are accumulation of oxidized phosphatidylcholines and signs of axonal pathology. In tissue culture, our studies show that ferrous iron, oxidized phosphatidylcholines and pro-inflammatory microglia are toxic to neurons (e.g. Dong et al., Nature Neurosci 2021). While we lack medications to antagonize iron or oxidized phosphatidylcholines in SELs, the toxicity of microglia may be ameliorated by repurposed hydroxychloroquine and the family of Bruton’s tyrosine kinase inhibitors (e.g. Yong, Neuron, Epub ahead of print).

Professor Taylor has been undertaking research into the genetic and environmental factors that are associated with the onset and progression of multiple sclerosis for more than 25 years. His work has focused on vitamin D and sunlight exposure as well as the role of infection with the Epstein Barr virus and other herpes viruses. He is a professorial research fellow at the Menzies Institute for Medical research University of Tasmania and currently holds an Australian National Health & Medical Research Council Leaders Fellowship. He has published over 380 papers and has an H Index of 70, his work has been cited more than 25000 times. He is currently an associate editor for the Journal of Neurology Neurosurgery and Psychiatry.

Abstract of Talk:

Epstein Barr Virus EBV is a ubiquitous human herpes virus that is known to be associated with several human illnesses including MS. Recent work has indicated that infection with EBV is an obligate risk factor for developing MS and that there may be molecular mimicry between EBV epitopes and CNS proteins. These important recent discoveries have raised the possibility of targeted therapies against EBV, or even vaccination against EBV as potential therapeutic options in the prevention or treatment of MS. This lecture will examine the current understanding of the role of EBV in MS causation and progression, the role of immunotherapy including T Cell therapies, and antivirals in the treatment of MS the potential role of anti-retroviral therapies in EBV control and the controversies surrounding the potential benefits and harm from an EBV Ivaccine

Dr Pin Fee Chong is currently with the department of Pediatrics, Graduate School of Medical Science, Kyushu University, Japan. His educational and academic appointments are as follows: 2006 M.D. Kyushu University, School of Medicine, Fukuoka, Japan 2006-2008 Internship in Medicine, Fukuoka Tokushukai Hospital 2008-2011 Residency in Pediatrics, Fukuoka Tokushukai Hospital 2011-2014 Residency in Child Neurology, Fukuoka Children’s Hospital 2014 -2021 Fukuoka Children’s Hospital (Dept of Child Neurology, Dept of General Pediatrics & Interdisciplinary Medicine) 2021- Current Position He is a certified board member of Japan Pediatric Society, Japanese Society of Child Neurology and Japan Epilepsy Society. His area of interest is in Pediatric neurological disorders, especially in inflammatory and infectious disease of the central nervous system. He has more than 30 publications in the area of pediatric neurological disorders including demyelinating disorders, encephalitis, acute flaccid myelitis, epilepsy, genetics, and others.

Abstract of Talk:

Over the past few years, autoantibodies against myelin oligodendrocyte glycoprotein (MOG-Abs) have been consistently identified in a variety of demyelinating syndromes. Although MOG-Abs were initially reported in children with acute disseminated encephalomyelitis (ADEM), the clinical spectrum of these MOG-Ab-associated disorder (MOGAD) is expanding and somehow differs between pediatric and adult patients. Recent studies using cell-based assays have demonstrated a higher frequency of MOG-Abs detection in pediatric than adult patients with acquired CNS demyelinating diseases. Typical pediatric MOGAD presentations usually show ADEM in younger, and optic neuritis and transverse myelitis in older children (age >9 years). A proportion of these children experience a relapsing disease course. Until recently, clinical and radiological evaluation has expanded the spectrum of MOGAD including those showing atypical features such as encephalitis- or leukodystrophy-like appearance and other unclassifiable phenotypes. While there is a lack of knowledge about the pathogenic roles of MOG, an increasing number of studies have shown that MOG is a protein that can elicit demyelinating immune response in animals. This review discusses the diversity in clinical phenotypes in pediatric MOGAD and present our recent data from both clinical and experimental perspectives.

Professor Russell Dale is a Paediatric Neurologist and clinical academic at the Children’s hospital at Westmead and University of Sydney. He is Head of Clinical School and Head of Speciality of Child and Adolescent Health of University of Sydney, and Clinical Director of the Kids Neuroscience Centre, a research group of 110 clinicians and scientists. He is an internationally recognised researcher in immune and autoimmune disorders of the brain, and neurodevelopmental and movement disorders of childhood. He has published 315 peer reviewed publications; his work has been cited 22,200 times and his H index is 76 (Google Scholar). His work has resulted in therapies for immune mediated brain disease being approved by government agencies and academic societies around the world, such as National institute for Clinical Excellence, American Academy of Neurology, and European League of Rheumatology. He has led international consensus guidelines for the treatment of autoimmune brain disease in children and been senior author on discovery papers of essential diagnostic biomarkers which are now part of routine clinical care around the world. He has been awarded over $18M in research funding and is a current NHMRC Leadership fellow (2021-5).

Abstract of talk:

A considered approach is required to the child or adolescent with acute or relapsing demyelination of the CNS. Firstly, the underlying clinical and syndrome and underlying pathophysiology differs in the very young child: The young child is more likely to present with acute disseminated encephalomyelitis (ADEM) or bilateral optic neuritis than an adult. In a young child with new onset CNS demyelination, it is more likely they have MOG antibody associated disease than multiple sclerosis. In the adolescent, multiple sclerosis becomes the more likely diagnosis in the child presenting with CNS demyelination. This distinction is essential, because the therapeutic approach is different between the autoantibody associated syndromes (MOGAD or AQP4 ab disease) and multiple sclerosis. Secondly, neuroinflammation is inherently problematic to the developing brain, and can result in disruption of synaptic connectivity, and consequently neurodevelopment. Hence, treating neuroinflammation speedily and adequately, is an important consideration. The cognitive sequelae of multiple sclerosis in adolescents, and neurodevelopmental problems such as ADHD after ADEM, are increasingly recognised. Thirdly, balancing the need for adequate immune modulation with side effects of treatment is important, to avoid harmful side effects to the young. Thankfully there is now good safety data regarding the use of immune therapies in children and adolescents with CNS demyelination, to aid the clinician in decision making. Fourthly, therapeutic compliance is a major consideration in the adolescent, and combination of respectful education plus empowerment is important.

Professor Ju-Hong Min is currently with the Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University Her areas of interest are in Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein-Associated Disorder, Demyelination, and Remyelination
Licenses and Certifications:
• 2000, License, Korean Medical Board (69696) • 2005, License, Korean Neurology Board • 2009, Certificate, Clinical Neurophysiology EMG & EP, The Korean Society for Clinical Neurophysiology
Membership: • Member, Korean Neurological Association • Member, American Academy Neurology • Member, Korean Society of Clinical Neurophysiology • Editorial Board Member, Korean Society of Neuromuscular disorder • Chair of Academics Committee, Korean Society of Pain & Autonomic Disorders (2020. 3~) • Editorial Board Member and Assistant administrator, Korean Society for Multiple Sclerosis • Chair of Academics Committee, Korean Society for Neuroimmunology (2020. 3~) • Advisory Board Member, Health Insurance Dispute Mediation Committee (2021. 1~)

Abstract of talk:

Immunosenescence is a process of immune dysfunction with aging and includes changes in the composition and function of lymphoid organs in the elderly. This is closely related to the development of autoimmunity and neurodegeneration and can contribute to co-morbidities in aging population. With increased life span and effective disease modifying therapies (DMTs), the number of elderly patients with CNS demyelinating diseases is growing. In addition, late-onset patients with such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody associated disorder (MOGAD) show different clinical characteristics, compared to early-onset patients, although the interactions of immunosenescence with pathomechanisms remain unclear. Particularly in MS, current DMTs reduce relapse activity and slow disease progression, but cannot prevent the accumulation of disability, which may be explained by the impact of immunosenescence on the immune system and disease progression. Moreover, most clinical trials for DMT were not designed focusing on aging patients and the risk of their comorbidities can negatively affect the disease course, which can make the therapeutic strategies more challenging in elderly patients with CNS demyelination.

Dr Ho Jin Kim is a consultant neurologist and principal scientist at the Research Institute and Hospital of National Cancer Center, Goyang Korea. He is also professor of Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science & Policy. Dr. Kim received his medical degree from Seoul National University where he also completed his residency training in neurology and clinical fellowship in multiple sclerosis (MS) and neuromuscular disease. Dr. Kim went on to pursue his academic research interest as a research fellow in neuroimmunology at the University of Southern California, Keck School of Medicine, Los Angeles, California, USA for a year. Then he spent four years as a senior fellow and staff researcher in MS and neuroimmunology at the Montreal Neurological Institute of McGill University, Montreal, Quebec, Canada. His major research interests lie in studying the development and application of biological assays to monitor the disease process and evaluate the response to novel therapeutics. His other research interests are in studying differences among various autoimmune inflammatory diseases of CNS including MS, neuromyelitis optica spectrum disorder and MOG-IgG associated disease in both clinical and radiological features as well as underlying pathogenesis. He is currently the Vice-President of PACTRIMS.

Abstract of talk:

Multiple sclerosis (MS), aquaporin-4 IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD) and myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) are three main relapsing form of autoimmune CNS diseases. In MS, the major burden of disability is thought to be a consequence of progressive disease independent of clinical attacks and new MRI activity. By contrast, attack-independent progression appears extremely rare in AQP4-IgG+ NMOSD and MOGAD, where disability is thought to derive almost exclusively from severe attacks, resulting in permanent tissue damage and poor recovery.

In the same vein, subclinical neuroaxonal damage in the absence of overt clinical attacks occurs in all stages of MS, while it is yet a matter of controversy in AQP4-IgG+ NMOSD and MOGAD. Identifying such an attack-independent tissue damage is essential, as it should be accounted for when evaluating treatment response, in order to achieve best clinical outcome. In this talk, I will review and discuss the current evidence on the occurrence of subclinical attack-independent tissue damage in patients with AQP4-IgG+ NMOSD and MOGAD.

Dr Jin Nakahara is based in Tokyo, Japan as a Professor and Chair of the Department of Neurology at Keio University School of Medicine. He is also a Deputy-Director of the Keio University Global Research Institute and a Visiting Professor of Kanazawa University. Professor Nakahara received his M.D. from the Keio University School of Medicine in 2003 and his Ph.D. from the Keio University Graduate School of Medicine in 2007. More than 70 articles in the field of neurology has been published in leading international journals, such as Developmental Cell, The Journal of Clinical Investigation, and Nature Neuroscience. He holds active memberships with many professional societies in Japan and abroad, and he is the current Director of the Japanese Society of Neuroimmunology. He also serves as a committee member of the Central Organizing Committee of Pan- Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS), a Delegate of the Japanese Society of Neurology, and a Councillor of the Japanese Society of Internal Medicine.

Abstract of talk:

The T2 lesion on magnetic resonance imaging (MRI) remains the most important paraclinical tool to identify demyelination and to diagnose multiple sclerosis (MS). However, the clinico-radiological paradox has been well recognized: There are only modest correlations between irreversible neurological disability and T2 lesion load in MS. Given the increasing number of available disease-modifying drugs (DMDs) with varying mechanisms of action, precise evaluation of individual MS immuno-pathology and neurodegeneration with advanced imaging may identify those who are at a risk of progressive disease course and ultimately lead to better choice of DMD to improve his/her prognosis. In the current lecture, current imaging modalities and their potential utility in MS will be reviewed and summarised.

Dr Lekha Pandit is the Professor of Neurology and Director of Centre for Advanced Neurological Research at Nitte University, Karnataka, India.
Honours:
• Fulbright Nehru scholar- Academic & Professional excellence- 2018
• Visiting Professor of Neurology, Harvard Medical School –2018 Sept-2019 Mar.
• Nominated member Central organizing committee of PACTRIMS (2015- present)
• Nominated member of International Medical Consortium of Guthy Jackson NMO Foundation, USA (2014- present)
• India representative of Multiple sclerosis International Federation Medical board (2014- 2018)
• Visiting Scholar, Addenbrookes hospital (MS genetic group), Cambridge, UK (2011-2012)
• Jacqueline Du Pre awardee (MSIF,UK)- 2012
• Research fellow- Demyelinating disorders- University of Newcastle upon Tyne (1995-1997)
Her area of Interest is in research and clinical management of CNS Autoimmune disorders and she has published over 150 peer reviewed papers and 16 chapters

Abstract of talk:

Vaccinations are integral to preparing patients for long term immunotherapy in autoimmune disorders such as multiple sclerosis. Vaccinations on one hand protect patients on disease modifying therapy against specific infections, but on the other, may have varied efficacy on these very patients by virtue of their underlying disease and concurrent medications. In addition, vaccination may trigger new / first attack of a demyelinating disorder. Geographically, susceptibility for specific infections vary and patients with multiple sclerosis may be on disease specific or “off label” therapies. These in turn increase the challenges in advocating vaccinations and especially timing of the latter in relation to ongoing therapy. The COVID-19 pandemic and COVID-19 vaccinations offer a good example for analysing the relationship between vaccinations, MS and immunotherapy. A review of real-life based evidence on vaccinations in MS patients on immunotherapy, including in a low- middle income set up will be presented.

Stephen Reddel is a staff specialist neurologist at Concord Repatriation & General Hospital Sydney, and consultant neurologist at the Brain & Mind Research Institute, University of Sydney. He trained in neurology at Royal Prince Alfred Hospital, Sydney, and at the Radcliffe Infirmary, Oxford, and has a PhD in the immunology of the Anti-Phospholipid Syndrome.
Stephen Reddel and Sean Riminton founded the first Australian neuroimmunology clinic at Concord Hospital, which specialises in the safe treatment of neurological conditions requiring immunotherapy, including multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and a host of rarer diseases.
He has a longstanding interest in clinical safety. This focus on safety has also included www.immunosuppressionscreen.net, and in 2014 the Alemtuzumab in MS Safety Study (AMS3), and multiple invited international presentations.
Dr Reddel’s academic appointment is Associate Professor, Sydney University where he has been involved in the neurology course development, ensuring standards of institutional sartorial elegance, online lectures and teaching of medical students, post graduate clinical training and post graduate research student supervision. He serves as the chair of the neurology working group for immunoglobulins and as the representative on the National Immunoglobulin Government Advisory Committee (NIGAC).
He has research interests in myasthenia gravis, examining the function of anti-MuSK antibodies and the homeostasis of the neuromuscular junction; in neuroimmunology and MS, and in neurogenetics including the muscular dystrophies and inherited neuropathies. Funding support in the last 5 years has included NH&MRC and the muscular dystrophy associations of the USA and NSW. He has published in journals including Brain, Annals of Neurology and Current Opinion in Neurology in this period.

Abstract of talk:

Autoimmunity in increasingly recognised as a cause of human and neurological disease, and unlike many diseases is treatable. The alloimmune response is not necessarily the same as the autoimmune response. The alloimmune response has prominent pattern recognition pathways (danger signals), innate immune system responses, and redundancy of pathways for defending against the pathogen.
Nevertheless as a general principle it is safer to assume that immunosuppressive drugs are likely to affect an alloimmune pathway that exists to fight an infection, at some time, somehow, somewhere. The absence of a signal in a selective population controlled randomised trial does not prove that such a drug is without risk in the real world application.
The recent global pandemic has illustrated how mechanisms of alloimmunity in the context of particular immunosuppression can anticipate what happens in a real test not seen in trials, for instance with pulsed anti-CD20 monoclonals in COVID-19 severity and vaccination responses. There are many other anticipatable risks for infection with our therapies that will be discussed.
The discussion of the infectious consequences of immunosuppression is not to undermine the excellent benefits of therapy, but it may influence choice, assist in screening and to diagnose events when they occur.

Professor Hartung is Professor of Neurology at Heinrich-Heine-University Düsseldorf, Honorary Professor, Brain and Mind Center, University of Sydney, Visiting Professor at Medical University Vienna and Palacky University Olomouc. Professor Hartung’s clinical and translational research interests are in the field of basic and clinical neuroimmunology, particularly exploring new treatments. He was President of ECTRIMS and is executive board member of the European Charcot Foundation. He has served on the SC and DMC of many phase 2 and 3 trials in MS, NMOSD, CIDP and GBS. He has authored more than 1060 articles in peer-reviewed journals and is a Highly Cited Researcher 2017, 2018, 2020. He is / has been on the editorial board of several journals.
Professor Hartung is a Fellow of the American Academy of Neurology, Corresponding Fellow of the American Neurological Association, Fellow and General Assembly member of the European Academy of Neurology, Honorary Member of the All Russian Neurological Society, Honorary Member of ECTRIMS, Honorary Member of the French Neurological Society, Honorary Member of the Polish Neurological Society, Member of the Association of British Neurologists and a Fellow of the Royal College of Physicians (London).

Abstract of talk:

Biomarkers encompass imaging and molecular biomarkers reflecting pathobiology, disease state and activity. Molecular biomarkers in MS can be determined in blood, CSF and saliva.
Fluid phase biomarkers serve different functions. They can be diagnostic, prognostic, indicate disease activity, and represent therapeutic response markers. Extensive research has been carried out using hypothesis and non-hypothesis driven approaches. I will review CSF and blood markers emphasizing the role of IgG and IgM oligoclonal bands, cytokines, chemokines, microRNAs and neurofilament light chains. The latter has emerged as the most robust fluid phase biomarkers in MS examined to date.

Heinz Wiendl studied medicine in Germany, Switzerland, and the USA, graduating in 1996. After working as a research fellow at the Institute of Neuroanatomy, Nuremberg, and the Max Planck Institute for Neurobiology and the Department of Neurology, Tuebingen, he became head of the clinical research group for multiple sclerosis (MS) in Wuerzburg in 2005 and acted as a vice-chair of the Department of Neurology. In 2010, he was recruited to the University Hospital Muenster as director of the Department of Neurology – Inflammatory Disorders of the Nervous System and Neurooncology. Since 2013, Prof. Wiendl serves as head of the Department of Neurology, Muenster – to which the Institute of Translational Neurology has been associated since 2018. His research focuses on inflammatory neurodegeneration and immune regulation and protection as well as monitoring MS and its therapy. His achievements have been recognized by both Sobek awards of the German Society for MS (DMSG) (2004; 2015). In 2017, he was appointed Honorary Professor at Sydney Medical School and in 2020 he received an honorary doctorate from the Medical Faculty of Masshad/Iran. Heinz Wiendl is a member of numerous scientific and academic advisory boards and expert panels, including editorial boards of international scientific journals in the fields of neurology, neurosciences, and immunology, as well as for societies, foundations, and project promoters. Currently, he is the speaker of the Collaborative Research Center 128 "Multiple Sclerosis", and speaker of the disease-related competence network
Multiple Sclerosis (KKNMS). He is the founder and principal investigator of the "Body and Brain Institute" Muenster, a prestigious research building funded by the German Federal Ministry.

Abstract of talk:

Current therapies for multiple sclerosis (MS) effectively reduce relapses and relapse-associated worsening caused by transient infiltration of peripheral immune cells into the CNS. However, they are less effective at slowing disability accumulation in both relapsing and progressive MS, possibly because they do not penetrate the blood-brain barrier (BBB) to act on CNS-resident innate immune cells that have been proposed to drive disability.
Bruton’s tyrosine kinase (BTK) is an intracellular signaling molecule regulating maturation, migration, survival, and activation of B cells and myeloid cells, particularly microglia. B cells and microglia are central players in MS immunopathogenesis and contribute to disease progression. As such, CNS-penetrant inhibitors of BTK (BTKis) hold promise to target adaptive and innate immunity concurrently on both sides of the BBB. Originally developed as a B-cell malignancy treatment, BTKis emerge as a promising therapeutic approach on the horizon of MS treatments. Currently, five BTKis are undergoing clinical trials in MS. These BTKis differ in selectivity, strength of BTK inhibition, binding mechanisms, and ability to modulate immune cells within the CNS. Here, BTK function in signaling pathways of different immune cells relevant to MS will be reviewed, and overview of preclinical data and clinical trial results will be provided.