A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed?

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.

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Amyotrophic lateral sclerosis: one or multiple causes?

Neurology International ◽

10.4081/ni.2011.e4 ◽

2011 ◽

Vol 3 (1) ◽

pp. 4 ◽

Cited By ~ 14

Author(s):

Aline Furtado Bastos ◽

Marco Orsini ◽

Dionis Machado ◽

Mariana Pimentel Mello ◽

Sergio Nader ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Motor Neurons ◽

Viral Infections ◽

Vigorous Physical Activity ◽

Disease Etiology ◽

New Research ◽

Lateral Sclerosis

The Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1), certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients.

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Glial Cells—The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment

Journal of Clinical Medicine ◽

10.3390/jcm9010261 ◽

2020 ◽

Vol 9 (1) ◽

pp. 261 ◽

Cited By ~ 2

Author(s):

Tereza Filipi ◽

Zuzana Hermanova ◽

Jana Tureckova ◽

Ondrej Vanatko ◽

Miroslava Anderova

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Current Knowledge ◽

Gene Mutations ◽

Cell Types ◽

In Vivo Models ◽

Cell Therapies ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease, which is characterized by the degeneration of motor neurons in the motor cortex and the spinal cord and subsequently by muscle atrophy. To date, numerous gene mutations have been linked to both sporadic and familial ALS, but the effort of many experimental groups to develop a suitable therapy has not, as of yet, proven successful. The original focus was on the degenerating motor neurons, when researchers tried to understand the pathological mechanisms that cause their slow death. However, it was soon discovered that ALS is a complicated and diverse pathology, where not only neurons, but also other cell types, play a crucial role via the so-called non-cell autonomous effect, which strongly deteriorates neuronal conditions. Subsequently, variable glia-based in vitro and in vivo models of ALS were established and used for brand-new experimental and clinical approaches. Such a shift towards glia soon bore its fruit in the form of several clinical studies, which more or less successfully tried to ward the unfavourable prognosis of ALS progression off. In this review, we aimed to summarize current knowledge regarding the involvement of each glial cell type in the progression of ALS, currently available treatments, and to provide an overview of diverse clinical trials covering pharmacological approaches, gene, and cell therapies.

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Lack of TNF-alpha receptor type 2 protects motor neurons in a cellular model of amyotrophic lateral sclerosis and in mutant SOD1 mice but does not affect disease progression

Journal of Neurochemistry ◽

10.1111/jnc.13154 ◽

2015 ◽

Vol 135 (1) ◽

pp. 109-124 ◽

Cited By ~ 16

Author(s):

Massimo Tortarolo ◽

Antonio Vallarola ◽

Dario Lidonnici ◽

Elisa Battaglia ◽

Francesco Gensano ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

Motor Neurons ◽

Receptor Type ◽

Tnf Alpha ◽

Cellular Model ◽

Mutant Sod1 ◽

Lateral Sclerosis

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An overview of motor unit number index reproducibility in amyotrophic lateral sclerosis

Iranian Journal of Neurology ◽

10.18502/ijnl.v18i3.1635 ◽

2019 ◽

Author(s):

Davood Fathi ◽

Shahriar Nafissi ◽

Shahram Attarian ◽

Christoph Neuwirth ◽

Farzad Fatehi

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Unit ◽

Motor Neurons ◽

Healthy Individuals ◽

Single Operator ◽

Electrophysiological Technique ◽

Lateral Sclerosis ◽

Research Studies

Motor unit number index (MUNIX) is an electrophysiological technique to give an estimate of functioning motor neurons in a muscle. For any given neurophysiological technique for the use in clinical or research studies, reproducibility between different operators and in a single operator in different times is one of the most important qualities, which must be evaluated and approved by different examiners and centers. After its introduction, testing the reproducibility of MUNIX was the aim of many studies to show this quality of the technique. In this review, we aimed to summarize all the studies, which have been performed up to now to approve MUNIX reproducibility in amyotrophic lateral sclerosis comparing healthy individuals.

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Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial

BMJ Open ◽

10.1136/bmjopen-2019-029449 ◽

2019 ◽

Vol 9 (11) ◽

pp. e029449 ◽

Cited By ~ 4

Author(s):

Berzenn Urbi ◽

Simon Broadley ◽

Richard Bedlack ◽

Ethan Russo ◽

Arman Sabet

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

Rating Scale ◽

Numeric Rating Scale ◽

Motor Neurone ◽

Double Blind ◽

Based Medicine ◽

Numeric Rating ◽

Lateral Sclerosis

IntroductionAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no known cure and with an average life expectancy of 3–5 years post diagnosis. The use of complementary medicine such as medicinal cannabis in search for a potential treatment or cure is common in ALS. Preclinical studies have demonstrated the efficacy of cannabinoids in extending the survival and slowing of disease progression in animal models with ALS. There are anecdotal reports of cannabis slowing disease progression in persons with ALS (pALS) and that cannabis alleviated the symptoms of spasticity and pain. However, a clinical trial in pALS with these objectives has not been conducted.Methods and analysisThe Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease trial is a randomised, double-blind, placebo-controlled cannabis trial in pALS conducted at the Gold Coast University Hospital, Australia. The investigational product will be a cannabis-based medicine extract (CBME) supplied by CannTrust Inc., Canada, with a high-cannabidiol-low-tetrahydrocannabinol concentration. A total of 30 pALS with probable or definite ALS diagnosis based on the El Escorial criteria, with a symptom duration of <2 years, age between 25 and 75years and with at least 70% forced vital capacity (FVC) will be treated for 6 months. The primary objective of the study is to evaluate the efficacy of CBME compared with placebo in slowing the disease progression measured by differences in mean ALS Functional Rating Scale-Revised and FVC score between the groups at the end of treatment. The secondary objectives are to evaluate the safety and tolerability of CBME by summarising adverse events, the effects of CBME on spasticity, pain, weight loss and quality of life assessed by the differences in mean Numeric Rating Scale for spasticity and Numeric Rating Scale for pain, percentage of total weight loss and ALS specific quality of life-Revised questionnaire.Ethics and disseminationThe study has been approved by the local Institutional Review Board. The results of this study will be published in a peer-reviewed journal.Trial registration numberNCT03690791

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Existing and Emerging Metabolomic Tools for ALS Research

Genes ◽

10.3390/genes10121011 ◽

2019 ◽

Vol 10 (12) ◽

pp. 1011 ◽

Cited By ~ 4

Author(s):

Christine Germeys ◽

Tijs Vandoorne ◽

Valérie Bercier ◽

Ludo Van Den Bosch

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Energy Metabolism ◽

Motor Neurons ◽

Therapeutic Strategies ◽

Metabolic State ◽

Advanced Technologies ◽

Novel Therapeutic Strategies ◽

Lateral Sclerosis ◽

Novel Therapeutic

Growing evidence suggests that aberrant energy metabolism could play an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Despite this, studies applying advanced technologies to investigate energy metabolism in ALS remain scarce. The rapidly growing field of metabolomics offers exciting new possibilities for ALS research. Here, we review existing and emerging metabolomic tools that could be used to further investigate the role of metabolism in ALS. A better understanding of the metabolic state of motor neurons and their surrounding cells could hopefully result in novel therapeutic strategies.

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Risk Factors and Emerging Therapies in Amyotrophic Lateral Sclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms20112616 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2616 ◽

Cited By ~ 21

Author(s):

Natalia Nowicka ◽

Jakub Juranek ◽

Judyta K. Juranek ◽

Joanna Wojtkiewicz

Keyword(s):

Risk Factors ◽

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Sod1 Gene ◽

Stem Cell Therapies ◽

Cell Therapies ◽

Emerging Therapies ◽

Emerging Treatments ◽

Phase Ii And Iii ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by a permanent degeneration of both upper and lower motor neurons. Many different genes and pathophysiological processes contribute to this disease, however its exact cause remains unclear. Therefore, it is necessary to understand this heterogeneity to find effective treatments. In this review, we focus on selected environmental and genetic risk factors predisposing to ALS and highlight emerging treatments in ALS therapy. Of numerous defective genes associated with ALS, we focus on four principal genes that have been identified as definite causes of ALS: the SOD1 gene, C9orf72, TDP-43, as well as the recently identified TBK1. We also provide up-to-date information on selected environmental factors that have historically been considered as key players in ALS development and pathogenesis. In parallel to our survey of known risk factors, we also discuss emerging ALS stem cell therapies and experimental medicines currently undergoing phase II and III clinical trials.

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Managing amyotrophic lateral sclerosis: Slowing disease progression and improving patient quality of life

Annals of Neurology ◽

10.1002/ana.21544 ◽

2009 ◽

Vol 65 (S1) ◽

pp. S17-S23 ◽

Cited By ~ 33

Author(s):

Benjamin Rix Brooks

Keyword(s):

Quality Of Life ◽

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

Lateral Sclerosis

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Are Amyotrophic Lateral Sclerosis Caregivers at Higher Risk for Health Problems?

Acta Médica Portuguesa ◽

10.20344/amp6590 ◽

2016 ◽

Vol 29 (1) ◽

pp. 56

Author(s):

Ana Catarina Pinho ◽

Edna Gonçalves

Keyword(s):

Quality Of Life ◽

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Health Care Professionals ◽

Large Body ◽

Holistic Approach ◽

Health Problems ◽

Physical Strain ◽

Lateral Sclerosis

Introduction: Amyotrophic lateral sclerosis is a rare neurodegenerative disease affecting motor neurons. Patients present with progressive physical impairment, respiratory failure being the main cause of death. A significant portion of patients presents neurobehavioral problems as well. As severe impairment occurs, patients become highly dependent and in general, their families assume the role of primary caregivers, exposing them to stress and other potential causes of disease like insomnia, physical strain from patients’ mobilization and changes on eating habits. The aim of this work is to understand if taking care of patients with amyotrophic lateral sclerosis increases disease and health problems on caregivers. Material and Methods: Comprehensive review of the literature published on the electronic databases PubMed and Scopus between 2010 and 2014. Results: Eighteen studies met the inclusion criteria. We found that amyotrophic lateral sclerosis caregivers have higher levels of burden, depression and anxiety with lower quality of life. This is associated to age and gender of caregivers, time spent caring, patients’ disability and neurobehavioral changes. Higher sense of support and spirituality on family seem to promote wellbeing. Discussion: On our work, we were able to understand that several factors have influenced caregivers’ quality of life and affect their health. Besides, we could understand that the outcomes studied are related between themselves and, as seen in some of the studies, related to patients’ quality of life itself. Consequently, it has become essential to adopt a holistic approach of these patients and their families, fighting the deteriorating risk factors and investing on health promoters. Conclusion: Despite the large body of research on family caregiving for amyotrophic lateral sclerosis patients, little has changed and the outcomes measured remain almost the same before and after 2010. The work indicates that caregivers have lower levels of health than the general population. Still additional research is required, in order to better understand and characterized the changes on caregivers’ health. It is nevertheless clear that health care professionals cannot ignore these health changes and need an approach focused not only on patients but also on caregivers.

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