Disease Mechanisms and Therapeutics for ALS: From Animal Models to Humans

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 3577

Special Issue Editor


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Guest Editor
School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi, Chiba 274-8555, Japan
Interests: amyotrophic lateral sclerosis; protein aggregation; endocytosis; metal homeostasis

Special Issue Information

Dear Colleagues,

Amyotrophic lateral sclerosis (ALS) is an incurable neuromuscular disease characterized by the selective death of motor neurons, resulting in progressive muscle atrophy. There is an emergent need to develop therapeutic strategies because of the modest effects of Riluzole and Edaravone, approved drugs for use in ALS, on the disease process. Success of developing animal models based on genetic discovery provides an understanding of molecular mechanisms underlying the pathogenesis of ALS as well as an opportunity to identify a potential candidate for treatment. Much effort has been devoted to discovering responsible genes for ALS such as SOD1, TARDBP, FUS, and C9ORF72. Nevertheless, our understanding of the disease process and the development of therapeutics for ALS can be still space for improvement.

This Special Issue welcomes original research with focus on a proof-concept study for a disease mechanism of ALS as well as a preclinical test using either mammalian or non-mammalian models carrying any responsible genes for ALS. Review articles that summarizes the ALS pathogenesis and/or preclinical outcomes based on animal models of ALS are also welcome. This Special Issue will advance our understanding of disease pathogenesis and develop therapeutic strategies for ALS with your research.

Dr. Eiichi Tokuda
Guest Editor

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Keywords

  • amyotrophic lateral sclerosis
  • animal models
  • preclinical study
  • disease mechanism
  • therapeutic strategy

Published Papers (1 paper)

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Review

14 pages, 245 KiB  
Review
Copper-ATSM as a Treatment for ALS: Support from Mutant SOD1 Models and Beyond
by Sara Nikseresht, James B.W. Hilton, Kai Kysenius, Jeffrey R. Liddell and Peter J. Crouch
Life 2020, 10(11), 271; https://doi.org/10.3390/life10110271 - 4 Nov 2020
Cited by 21 | Viewed by 3199
Abstract
The blood–brain barrier permeant, copper-containing compound, CuII(atsm), has successfully progressed from fundamental research outcomes in the laboratory through to phase 2/3 clinical assessment in patients with the highly aggressive and fatal neurodegenerative condition of amyotrophic lateral sclerosis (ALS). The most compelling [...] Read more.
The blood–brain barrier permeant, copper-containing compound, CuII(atsm), has successfully progressed from fundamental research outcomes in the laboratory through to phase 2/3 clinical assessment in patients with the highly aggressive and fatal neurodegenerative condition of amyotrophic lateral sclerosis (ALS). The most compelling outcomes to date to indicate potential for disease-modification have come from pre-clinical studies utilising mouse models that involve transgenic expression of mutated superoxide dismutase 1 (SOD1). Mutant SOD1 mice provide a very robust mammalian model of ALS with high validity, but mutations in SOD1 account for only a small percentage of ALS cases in the clinic, with the preponderant amount of cases being sporadic and of unknown aetiology. As per other putative drugs for ALS developed and tested primarily in mutant SOD1 mice, this raises important questions about the pertinence of CuII(atsm) to broader clinical translation. This review highlights some of the challenges associated with the clinical translation of new treatment options for ALS. It then provides a brief account of pre-clinical outcomes for CuII(atsm) in SOD1 mouse models of ALS, followed by an outline of additional studies which report positive outcomes for CuII(atsm) when assessed in cell and mouse models of neurodegeneration which do not involve mutant SOD1. Clinical evidence for CuII(atsm) selectively targeting affected regions of the CNS in patients is also presented. Overall, this review summarises the existing evidence which indicates why clinical relevance of CuII(atsm) likely extends beyond the context of cases of ALS caused by mutant SOD1. Full article
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