title: Modelling and treating amyotrophic lateral sclerosis through induced-pluripotent stem cells technology.
abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease affecting primarily the population of motor neurons, even though a non-cell autonomous component, involving neighbouring non-neuronal cells, is more and more described. Despite 140 years of disease experience, still no efficient treatment exists against ALS. The inability to readily obtain the faulty cell types relevant to ALS has impeded progress in drug discovery for decades. However, the pioneer work of Shinya Yamanaka in 2007 in the stem cell field was a real breakthrough. Recent advances in cell reprogramming now grant access to significant quantities of CNS disease-affected cells. Induced pluripotent stem cells (iPSc) have been recently derived from patients carrying mutations linked to familial forms of ALS as well as from sporadic patients. Precise and mature protocols allow now their differentiation into ALS-relevant cell subtypes; sustainable and renewable sources of human motor neurons or glia are being available for ALS disease modelling, drug screening or for the development of cell therapies. In few years, the proof-of-concept was made that ALS disease-related phenotypes can be reproduced with iPSc and despite some remaining challenges, we are now not so far to provide platforms for the investigation of ALS therapeutics. This paper also reviews the pioneering studies regarding the applicability of iPSc technology in ALS animal models. From modest slowing down of ALS progression to no severe adverse effects, iPSc-based cell therapy resulted in promising premises in ALS preclinical paradigms, although long-term surveys are highly recommended.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bohl
authors.forename: Roland
authors.initials: R
authors.lastname: Pochet
authors.forename: Dinko
authors.initials: D
authors.lastname: Mitrecic
authors.affiliation: Laboratory Neurodegeneration and Regeneration, URPhyM - NARILIS, Faculty of Medicine, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium. charles.nicaise@unamur.be.
authors.forename: Charles
authors.initials: C
authors.lastname: Nicaise
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000628:therapy*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming; D004195:Disease Models, Animal; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D009046:Motor Neurons / Q000637:transplantation; D033581:Stem Cell Transplantation