Amyotrophic Lateral Sclerosis Clinical Trials

Author(s):  
Katharine A. Nicholson ◽  
James D. Berry

The current state of amyotrophic lateral sclerosis (ALS) trial design is best understood within the context of ALS research over the past quarter century. Before the early 1990s, trials in ALS were typically small and clinical trial methodology was less rigorous than it is today. With the discovery of the SOD1 gene mutation in the early 1990s, a new era of excitement and innovation for ALS research began. Since then, the number of ALS trials has steadily increased and trial design and methodology has become increasingly sophisticated.

2021 ◽  
Vol 11 (7) ◽  
pp. 671
Author(s):  
Oihane Pikatza-Menoio ◽  
Amaia Elicegui ◽  
Xabier Bengoetxea ◽  
Neia Naldaiz-Gastesi ◽  
Adolfo López de Munain ◽  
...  

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system. Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS. Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS. Moreover, a fine-tuning balance between biosynthetic and atrophic pathways is necessary to induce myogenesis for muscle tissue repair. Compromising this response due to primary metabolic abnormalities in the muscle could trigger defective muscle regeneration and neuromuscular junction restoration, with deleterious consequences for MNs and thereby hastening the development of ALS. However, it remains puzzling how backward signaling from the muscle could impinge on MN death. This review provides a comprehensive analysis on the current state-of-the-art of the role of the skeletal muscle in ALS, highlighting its contribution to the neurodegeneration in ALS through backward-signaling processes as a newly uncovered mechanism for a peripheral etiopathogenesis of the disease.


2021 ◽  
pp. SP510-2021-87
Author(s):  
Jiandong Xu ◽  
Clive Oppenheimer ◽  
James O. S. Hammond ◽  
Haiquan Wei

AbstractChina ishas a rich record of Holocene volcanism that is relatively little known outside the country. It is encountered in home to a number of volcanoes that have erupted in the Holocene. These range from large stratovolcanoes in the northeast, linked to subduction of the pPacific plate (e.g., Changbaishan); in , more diffuse volcanismsmaller volcanoes on the edges of the TibetTibetan margin, linked toassociated with the collision of India and AEurasia (e.g., Tengchong, Ashishan), and more isolated regions of volcanismcentres possibly linked topossibly resulting from mantle upwelling (e.g., volcanoes in Hainan island). This makes China a natural laboratory for studyingstudies of intraplate volcanism, yet the study of volcanology in China is young, with a significant increase in research only over the last 25 yearsand significant progress in understanding its nature and origins has been made over the past quarter century. To highlight recent advances and the current state of knowledge, thisHere, we introduce the first publication in English to provide a comprehensive survey of the state of knowledge and research highlights. special volume presents the first compilation of research on the active volcanoes of China in English. This first paper introduces the book, which coversAccordingly, we provide an overview of the dynamics, geology, geochemistry, volcanic histories and geophysical studies of the 14 volcanoesvolcanic areas that have erupted in theassociated with Holocene documented thus far. Our hope is that this special publication acts as The special publication represents a benchmark reference on the topic but, as importantly, we hope it will stimulatea resource to allow new, international collaborations to be developed to help understandaimed at deepening our understanding of the origins, history, hazards and associated risks from future eruptions of China's volcanoes.


US Neurology ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. 47 ◽  
Author(s):  
Said R Beydoun ◽  
Jeffrey Rosenfeld

Edaravone significantly slows progression of amyotrophic lateral sclerosis (ALS), and is the first therapy to receive approval by the Food and Drug Administration (FDA) for the disease in 22 years. Approval of edaravone has marked a new chapter in pharmaceutical development since the key trial included a novel strategic clinical design involving cohort enrichment. In addition, approval was based on clinical trials that had a relatively small patient number and were performed outside of the US. Edaravone was developed through a series of clinical trials in Japan where it was determined that a well-defined subgroup of patients was required to reveal a treatment effect within the study period. Amyotrophic lateral sclerosis is associated with wide-ranging disease heterogeneity (both within the spectrum of ALS phenotypes as well as in the rate of progression). The patient cohort enrichment strategy aimed to address this heterogeneity and should now be considered as a viable, and perhaps preferred, trial design for future studies. Future research incorporating relevant biomarkers may help to better elucidate edaravone’s mechanism of action, pharmacodynamics, and subsequently ALS phenotypes that may preferentially benefit from treatment. In this review, we discuss the edaravone clinical development program, outline the strategic clinical trial design, and highlight important lessons for future trials.


2019 ◽  
Vol 3 (3) ◽  
pp. 269-279
Author(s):  
Kelley C. O’Donnell ◽  
Sarah E. Mennenga ◽  
Michael P. Bogenschutz

Background and aims Given the enormous global burden of depressive illness, there is an urgent need to develop novel and more effective treatments for major depressive disorder (MDD). Recent findings have suggested that psychedelic drugs may have a role in the treatment of depressive symptoms, and a number of groups are in the process of developing protocols to study this question systematically. Given the subjective quality of both the psychedelic experience and depressive symptomatology, great care must be taken when designing a protocol to study the clinical efficacy of psychedelic drugs. This study will discuss many factors to consider when designing a clinical trial of psilocybin for MDD. Methods We provide a thorough review of pertinent research into antidepressant clinical trial methodology and review practical considerations that are relevant to the study of psychedelic-assisted treatment for depression. Results We discuss participant selection (including diagnostic accuracy, exclusion criteria, characteristics of the depressive episode, and the use of concurrent medications), study interventions (including dosing regimens, placebo selection, non-pharmacological components of treatment, and the importance of blinding), trial duration, outcome measures, and safety considerations. Conclusions Careful and transparent study design and data analysis will maximize the likelihood of generating meaningful, reproducible results, and identifying a treatment-specific effect. Meeting the highest standards for contemporary trial design may also broaden the acceptance of psychedelic research in the scientific community at large.


2013 ◽  
Vol 34 (6) ◽  
pp. 1709.e3-1709.e5 ◽  
Author(s):  
Rosanna Tortelli ◽  
Francesca Luisa Conforti ◽  
Rosa Cortese ◽  
Eustachio D'Errico ◽  
Eugenio Distaso ◽  
...  

The concept of advocacy literally means to speak for someone. Rooted in law, the term has been increasingly used in medical and patient-related contexts in the past years. This book focuses on advocacy activities in the field of neurology. Neurology deals with heterogeneous and diverse populations of patients, who suffer from disability, chronic, and often progressive diseases. The complex characteristics of neurological diseases yield exceptional challenges to plan for and implement advocacy activities on all levels. All stakeholders are challenged to provide the support patients need; advocacy facilitates this process and bundles efforts to reach the objective of the advocacy task. Building on the premise that advocacy goes beyond merely theoretical claims, this book collects and organizes advocacy approaches in practice. Thereby, we draw on different dimensions of ‘advocacy in neurological practice’ and discuss implications for management, healthcare, planning, and policymaking. We place special emphasis on what advocacy means for several different diseases, such as amyotrophic lateral sclerosis (ALS), brain tumours, MS, epilepsy among others. Contributions include best practices, lessons learnt, and tools to be used. The main goal of this book is to raise awareness for advocacy in neurology and empower readers to plan for and implement appropriate activities. In advocacy, anyone can be both an advocate and an advocatee. This book offers a seminal contribution for anyone who is pursuing or intending to pursue advocacy in neurology and related fields.


2013 ◽  
Vol 47 (5) ◽  
pp. 751-757 ◽  
Author(s):  
E. V. Lysogorskaia ◽  
A. V. Rossokhin ◽  
N. Yu. Abramycheva ◽  
M. N. Zakharova ◽  
S. N. Illarioshkin

2003 ◽  
Vol 206 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Nam-Hee Kim ◽  
Hyun-Jung Kim ◽  
Manho Kim ◽  
Kwang-Woo Lee

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