Spectrums of Amyotrophic Lateral Sclerosis. Группа авторов

Health Sciences, Macquarie University, Sydney, New South Wales, Australia

      Thomas E. Marler, College of Natural and Applied Sciences, University of Guam, Mangilao, Guam, USA

      Amber L. Marriott, CNS Contract Research Corp, Charlottetown, Prince Edward Island, Canada

      Luke McAlary, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia; Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia

      Jessica R. Morrice, Experimental Medicine Program, University of British Columbia, Vancouver, British Columbia, Canada

      Marco Morsch, Motor Neuron Disease Research Centre, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia

      Alex Parker, Department of Neuroscience, University of Montréal, Montréal, Québec, Canada; Centre de recherche du centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada

      Rowan A.W. Radford, Motor Neuron Disease Research Centre, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia

      Jay P. Ross, Department of Human Genetics, McGill University, Montréal, Québec, Canada; Montréal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada

      Guy A. Rouleau, Department of Human Genetics, McGill University, Montréal, Québec, Canada; Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada

      Mario Sabatelli, Sezione di Medicina Genomica, Dipartimento Scienze della Vita e Sanità Pubblica, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy

      Kristiana Salmon, Montreal Neurological Institute and Hospital, Montréal, Québec, Canada

Natalie M. Scherer, Motor Neuron Disease Research Centre, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia

      Christopher A. Shaw, Experimental Medicine Program, University of British Columbia, Vancouver, British Columbia, Canada; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada

      Ted Stehr, ALS Society of BC Director, and person living with ALS

      Andres Vidal‐Itriago, Motor Neuron Disease Research Centre, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia

      Justin J. Yerbury, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia; Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia

Foreword

       Charles Krieger

       Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada

       Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

       Division of Neurology, Vancouver Coastal Health, Vancouver, British Columbia, Canada

      The past decade or so has seen a substantial increase in the extent of research directly or indirectly related to amyotrophic lateral sclerosis (ALS). Unfortunately, this research has had limited impact on the clinical course of patients with ALS, suggesting that in many fundamental ways we do not really understand this disease. Numerous observations still defy a clear explanation. For instance, how is it that mutations in various genes, seemingly without a clear interaction in a signaling cascade or pathophysiologic mechanism, all result in a disease with a superficially similar phenotype, a phenotype that is shared with patients where no known gene mutations are present? How is it that the rate of progression of ALS is so rapid and unresponsive to modulation in some patients, yet a lucky few will have the disease course slow substantially? Why are there specific patterns of nervous system involvement in ALS such as “classic” ALS (Charcot type), bulbar ALS (perhaps better described by the original name of “glosso‐labio‐pharyngeal paralysis”), progressive muscular atrophy, and primary lateral sclerosis? What is the relation between the loss of motoneurons and their axons and the progressive decline in corticospinal and other descending connections? What is the basis of fasciculations? How does ALS “spread” so rapidly in the nervous system? These and other questions remain unanswered.

      It is also interesting to look back at how our view of ALS research has changed over time. A clinician or scientist of 25 or 50 years ago would not have seen much investigation into ALS. To those of us who were involved with ALS at that time, the disease appeared neglected. Potentially, to a researcher investigating ALS 50 years ago, it also might have seemed that a treatment for this disease would be relatively straightforward, compared to the treatment of other neurological diseases like Alzheimer's disease or Parkinson's disease. ALS was characterized by the loss of neuronal populations that were well studied, even decades ago, and affected cells might be amenable to the delivery of intrathecal or intramuscular treatment to augment the health of dying neurons and so prolong patient survival.

How times have changed! Instead of being a neglected disorder, there has been considerable scientific and public interest in ALS, due not only to events like the Ice Bucket Challenge, but also to social media and increasing public awareness. Second, the initial hopes that the disease would turn out to be treatable and responsive to trophic molecules and other factors that would improve the “metabolism” of motoneurons have not yet borne fruit. In retrospect, it seems clear that given the complexity of motoneuron physiology, the difficulty of successful treatment may not have been fully appreciated. Furthermore, the scientific community generally has woken up to the challenge that ALS poses, and many labs around the world are investigating aspects of the disease: the genetics of ALS, the relation between viruses and ALS, RNA‐binding proteins, risk genes and environmental toxins, as well as other topics that are reviewed in the present volume.

      We can only hope that this new volume will be a stimulus for continued research on ALS and result in insights into this enigmatic, frustrating, and tragic illness.

Preface

      Source: Reproduced with the permission of Ted Stehr.

      All humanity is on a train speeding through time. The name of the train is life. And like a train you might see in India, it's covered with people, inside and out. People inside are seated in different classes and are engaged in all manner of activities. The people on the roof would love to be inside. They are the sick. The wind buffets them, the rain drenches them, and the sun beats down on them. And each time the train jostles or turns, they have to quickly cling on to prevent them from sliding off and ending their journey.

      The terminally ill cling precariously to the side of the train. They try to find perches on the thin window ledges or doorway openings. Some of them have ALS. They are exhausted from the relentless wind and weather, from standing, and from the strain of grasping whatever they can to keep from falling. Often the exhaustion is so great that they feel it might be easier to just let go. But something miraculous happens. People inside the train have given up their seats, walked over to the windows, and put arms around those desperate people. They say, “Don't worry, I have you. Relax for