Spinal Muscular Atrophy Modeling and Treatment Advances by Induced Pluripotent Stem Cells Studies.

ABSTRACT

Spinal Muscular Atrophy (SMA) is a neurodegenerative disease characterized by specific and predominantly lower motor neuron (MN) loss. SMA is the main reason for infant death, while about one in 40 children born is a healthy carrier. SMA is caused by decreased levels of production of a ubiquitously expressed gene the survival motor neuron (SMN). All SMA patients present mutations of the telomeric SMN1 gene, but many copies of a centromeric, partially functional paralog gene, SMN2, can somewhat compensate for the SMN1 deficiency, scaling inversely with phenotypic harshness. Because the study of neural tissue in and from patients presents too many challenges and is very often not feasible; the use of animal models, such as the mouse, had a pivotal impact in our understanding of SMA pathology but could not portray totally satisfactorily the elaborate regulatory mechanisms that are present in higher animals, particularly in humans. And while recent therapeutic achievements have been substantial, especially for very young infants, some issues should be considered for the treatment of older patients. An alternative way to study SMA, and other neurological pathologies, is the use of induced pluripotent stem cells (iPSCs) derived from patients. In this work, we will present a wide analysis of the uses of iPSCs in SMA pathology, starting from basic science to their possible roles as therapeutic tools.