scholarly journals MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design

2021 ◽  
Author(s):  
Björn Oskarsson ◽  
Nicholas Maragakis ◽  
Richard S Bedlack ◽  
Namita Goyal ◽  
Jenny A Meyer ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cell Activation ◽  
Phosphodiesterase Inhibition ◽  
Double Blind ◽  
Multicenter Phase ◽  
Glial Cell Activation ◽  
Motor Neuron Loss ◽  
Significant Effort ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibudilast) has demonstrated neuroprotective action by various mechanisms: inhibition of proinflammatory cytokines and macrophage migration inhibitory factor, phosphodiesterase inhibition, and attenuation of glial cell activation in models of ALS. Early-phase studies suggest that MN-166 may improve survival outcomes and slow disease progression in patients with ALS. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study in ALS. This study is designed to evaluate the pharmacokinetics, safety and tolerability and assess the efficacy of MN-166 on function, muscle strength, quality of life and survival in ALS.

scholarly journals 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 ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e029449 ◽  
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

Targeting abnormal Nrf2/HO-1 signaling in amyotrophic lateral sclerosis: Current Insights on drug targets and influences on neurological disorders

2021 ◽  
Vol 21 ◽  
Author(s):  
Elizabeth Minj ◽  
Rajeshwar Kumar Yadav ◽  
Sidharth Mehan
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Drug Targets ◽  
Cell Activation ◽  
Symptomatic Relief ◽  
Neuronal Cell ◽  
Related Factor ◽  
Glial Cell Activation ◽  
Lateral Sclerosis

: The nuclear erythroid 2-related-factor (Nrf2) transcription factor/hemoxygenase 1 (HO-1) is a key regulator of an important neuroprotection response by driving the interpretation of various cytoprotective gene to encode for antiinflammatory, anti-oxidant, and detoxifying proteins. Various studies investigated that the upregulation of Nrf2/HO-1 has become the potential therapeutic approach in amyotrophic lateral sclerosis (ALS). As amyotrophic lateral sclerosis is a motor neuron disease in which there is a progressive loss of upper motor neuron and lower motor neurons of the motor cortex, brain stem, and corticospinal tract. As a result of this upregulation of Nrf2/HO-1 indicates that in brain antioxidant capacity is reinforced. Further, this shows a cytoprotective effect against oxidative stress in amyotrophic lateral sclerosis. A study reported functions associated with the Nrf2/HO-1 in the neuronal cell, oligodendrocytes, microglia, and astrocytes. Although ALS's pathogenesis is not yet clear but compelling, the evidence shows any dysfunction in the brain such as mitochondrial dysfunction, protein aggregation, glial cell activation, excitotoxicity, and apoptosis gives ALS like symptoms. In this review, we have mainly focused on detailing the downregulation of Nrf2/HO-1, which may be the prime reason and may further serve as a pathological hallmark for ALS development. As surveyed, there are limited target-based interventions that only provide symptomatic relief but do not cure the disease completely. Dysregulation of the Nrf2/HO-1 signaling pathway leads to many physiological changes contributing to neurological conditions, including ALS. Based on the above view, we summarized the combined role of Nrf2/HO-1 signaling in ALS and explored potential therapeutic strategies for disease improvement through pathway modulators.

scholarly journals Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial

2014 ◽  
Vol 13 (11) ◽  
pp. 1083-1091 ◽  
Author(s):  
Merit E Cudkowicz ◽  
Sarah Titus ◽  
Marianne Kearney ◽  
Hong Yu ◽  
Alexander Sherman ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Controlled Trial ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Double Blind Placebo ◽  
Multi Stage ◽  
Lateral Sclerosis

scholarly journals Independent home use of a brain-computer interface by people with amyotrophic lateral sclerosis

Neurology ◽  
2018 ◽  
Vol 91 (3) ◽  
pp. e258-e267 ◽  
Author(s):  
Jonathan R. Wolpaw ◽  
Richard S. Bedlack ◽  
Domenic J. Reda ◽  
Robert J. Ringer ◽  
Patricia G. Banks ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Amyotrophic Lateral Sclerosis ◽  
Brain Computer Interface ◽  
Computer Interface ◽  
It Use ◽  
Technical Problems ◽  
Rapid Disease Progression ◽  
And Performance ◽  
Lateral Sclerosis

ObjectiveTo assess the reliability and usefulness of an EEG-based brain-computer interface (BCI) for patients with advanced amyotrophic lateral sclerosis (ALS) who used it independently at home for up to 18 months.MethodsOf 42 patients consented, 39 (93%) met the study criteria, and 37 (88%) were assessed for use of the Wadsworth BCI. Nine (21%) could not use the BCI. Of the other 28, 27 (men, age 28–79 years) (64%) had the BCI placed in their homes, and they and their caregivers were trained to use it. Use data were collected by Internet. Periodic visits evaluated BCI benefit and burden and quality of life.ResultsOver subsequent months, 12 (29% of the original 42) left the study because of death or rapid disease progression and 6 (14%) left because of decreased interest. Fourteen (33%) completed training and used the BCI independently, mainly for communication. Technical problems were rare. Patient and caregiver ratings indicated that BCI benefit exceeded burden. Quality of life remained stable. Of those not lost to the disease, half completed the study; all but 1 patient kept the BCI for further use.ConclusionThe Wadsworth BCI home system can function reliably and usefully when operated by patients in their homes. BCIs that support communication are at present most suitable for people who are severely disabled but are otherwise in stable health. Improvements in BCI convenience and performance, including some now underway, should increase the number of people who find them useful and the extent to which they are used.

Quality-of-Life Assessments That Can Be Used for Patients Diagnosed With Amyotrophic Lateral Sclerosis: A Scoping Review

2021 ◽  
Vol 75 (Supplement_2) ◽  
pp. 7512500033p1
Author(s):  
Addie Broom ◽  
Hannah Prescott ◽  
Mallorie Savage ◽  
Addie Broom ◽  
Emily Crawford ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Amyotrophic Lateral Sclerosis ◽  
Scoping Review ◽  
Lateral Sclerosis

User Centered Approach to the Supra-Functional Needs of People Living with Amyotrophic Lateral Sclerosis (ALS)

2020 ◽  
Author(s):  
Deana McDonagh ◽  
Kayla Arquines ◽  
Elizabeth T. Hsiao-Wecksler ◽  
Mahshid Mansouri ◽  
Girish Krishnan ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Design Thinking ◽  
Healthcare Management ◽  
User Centered Design ◽  
Emotional Needs ◽  
Empathic Understanding ◽  
The Individual ◽  
Lateral Sclerosis ◽  
User Centered

Abstract User-centered design relies upon the appreciation that assistive technology device solutions need to include the functional and supra-functional (e.g., emotional, social, cultural) needs of users. Developing solutions without basing decision-making on both quantitative (functional) and qualitative (supra-functional) needs can lead to imbalanced devices, services, and/or environments. Satisfying both functional and supra-functional needs is the foundation of user-centered design, which in itself relies upon empathic understanding of the person that one is aiming to serve. This paper presents a study of the lived experiences of people living with Amyotrophic Lateral Sclerosis, their caregivers, and members of the healthcare management team from a human-centered perspective in the pursuit of pain points, deeper understanding of the emotional needs, and revelation of opportunities for improving quality of life and human experience through more user-centered design. We focus on user-centered design-thinking research tools (e.g., mood boards, journey maps, personas) to (a) understand the authentic experience of the individual in their vernacular and their terminology, and (b) to support a data rich conversation that focuses upon both functional and supra-functional needs to highlight opportunities for design interventions).

scholarly journals Amyotrophic lateral sclerosis: one or multiple causes?

2011 ◽  
Vol 3 (1) ◽  
pp. 4 ◽  
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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