CNS Drugs

, Volume 30, Issue 3, pp 227–243 | Cite as

Advances in the Development of Disease-Modifying Treatments for Amyotrophic Lateral Sclerosis

  • Diane MoujalledEmail author
  • Anthony R. White
Review Article


Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset, neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Over recent years, numerous genes ha ve been identified that promote disease pathology, including SOD1, TARDBP, and the expanded hexanucleotide repeat (GGGGCC) within C9ORF72. However, despite these major advances in identifying genes contributing to ALS pathogenesis, there remains only one currently approved therapeutic: the glutamate antagonist, riluzole. Seminal breakthroughs in the pathomechanisms and genetic factors associated with ALS have heavily relied on the use of rodent models that recapitulate the ALS phenotype; however, while many therapeutics have proved to be significant in animal models by prolonging life and rescuing motor deficits, they have failed in human clinical trials. This may be due to fundamental differences between rodent models and human disease, the fact that animal models are based on overexpression of mutated genes, and confounding issues such as difficulties mimicking the dosing schedules and regimens implemented in mouse models to humans. Here, we review the major pathways associated with the pathology of ALS, the rodent models engineered to test efficacy of candidate drugs, the advancements being made in stem cell therapy for ALS, and what strategies may be important to circumvent the lack of successful translational studies in the clinic.


Amyotrophic Lateral Sclerosis Motor Neuron Amyotrophic Lateral Sclerosis Patient Riluzole Mutant SOD1 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards


DM is supported by an Alzheimer’s Australia Dementia Research fellowship (AADRF) and funding from the Motor Neuron Disease Research Institute of Australia (MNDRIA). ARW is supported by an Australian Research Council Future Fellowship and The National Health and Medical Research Council of Australia.

Conflict of interest

Patent protection has previously been sought by the University of Melbourne for the use of bis(thiosemicarbazones) for treatment of diseases. ARW is a co-inventor on the patent application PCT/AU2007/001792 that is the subject of a commercialization contract between the University and a private company. The company has neither funded nor contributed to research described in this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Pathology and Florey Institute of Neuroscience and Mental HealthThe University of MelbourneMelbourneAustralia

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