Cell-based Research and Therapy for Amyotrophic Lateral Sclerosis: Promises and Challenges

ABSTRACT 

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which leads to a progressive degeneration of motoneurons. Since the pharmacological options available provide only a slight increase in life expectancy, cell therapy is emerging as a promising therapeutic alternative for ALS. A growing body of evidence from studies using genetically engineered ALS animal models demonstrate the safety and efficacy of therapies based on different cell types such as mononuclear cells, neural progenitors, and mesenchymal stem cells. Despite the encouraging results in preclinical studies, cell therapy-based clinical trials for ALS have achieved only modest results so far, probably due to the genotypic variations seen among ALS patients, which is difficult to reproduce in animal models. The advent of induced pluripotent stem cells (iPSCs) has enabled the development of patient-specific cell lines, a valuable tool to investigate in vitro molecular mechanisms of the disease and therapies in different genetic backgrounds. The applications of ALS iPSCs and their future therapeutic potential are also briefly discussed in this chapter.