Advances in Spinal Muscular Atrophy - Volume II

Spinal muscular atrophy (SMA) is defined as an autosomal recessive motor neuron disorder with an estimated incidence of 1 in 6,000 to 1 in 10, 000 live births and a carrier frequency of 1/40 to 1/60. SMA is the leading inherited cause of infant mortality. This disease is characterized by predominant proximal muscle weakness and atrophy and neurodegeneration. The SMA field has advanced remarkably since the discovery of the causative survival motor neuron 1 gene (SMN1) in 1995. Over the past 30 years, intense efforts have elucidated the molecular mechanisms of the SMN gene, which have led to the approval of three disease-modifying therapies targeting an increase in SMN protein levels, since 2016. These treatments provide significant benefit to SMA patients. However, none of these high-priced therapies represents a cure for SMA. These gene-based therapies have shifted the natural history of SMA and increased the variability of SMA phenotypes. The variability of SMA phenotype and treatment outcomes requires the development of various SMA models. The field is calling for more targeted and individualized approaches. Nevertheless, novel treatment strategies toward the cure of SMA require a full understanding of the mechanisms of SMA pathology.

SMA is widely recognized as a lower motor neuron disease. Hence, most studies focus on the pathology of spinal cord motor neurons and their targeted muscles. However, growing evidence from patients and animal models demonstrates the multisystem nature of SMA, indicating that SMA is a multisystem disorder. The ubiquitous SMN protein has broad roles across many cell types and physiological systems. SMA affects skeletal muscle, heart, liver, kidney, pancreas, spleen, and immune system, besides the nervous system. To deepen and eventually fully understand the mechanism of SMA pathology, a systematic study of the CNS beyond the spinal cord and other systems is crucial.

This topic aims to compile studies of SMA pathology in all cell types and other motor control regions of the CNS in addition to the spinal cord. Additionally, studies in peripheral organs and tissues, and the development of novel SMA animal models and treatment approaches are also welcomed. The goal of this collection is to promote the study of mechanisms of SMA pathology and novel treatment approaches. We hope these kinds of studies will advance the understanding of the SMA pathology and lead to a cure for the disease. Original research, case reports, and review articles are welcome in this collection.

The first volume of this Research Topic can be found at: Advances in Spinal Muscular Atrophy