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. The SMA field has advanced remarkably since the discovery of the causative survival motor neuron 1(SMN1) gene in 1995. Over the past less than 30 years, intense efforts have elucidated the molecular mechanisms of the SMN gene, which led to the approval of 3 disease-modifying therapies targeting an increase of SMN protein levels since 2016 in the United States. However, none of these high price therapies represents a cure for SMA. There also remain some major limitations and concerns including non-responders, outcome variability, and unknown long-term effects from real-world data. Novel treatment strategies towards the cure of SMA require fully understanding the mechanisms of the SMA pathology.
SMA is widely recognized as a lower motor neurons disease. Hence, most of the 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 may be 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 better and eventually fully understand the mechanisms of SMA pathology, a systematic study of CNS beyond the spinal cord and other systems is crucial.
The aim of this topic is to advocate studies of SMA pathology in all cell types and other motor control regions of CNS in addition to the spinal cord, and the studies in peripheral organs and tissues in both patients and models. For better understanding the mechanisms of SMA pathology, the goal of this collection is to answer key questions, including, but not limited to, 1) What’s the cellular neuropathology of other types of cells including interneurons and glia in the spinal cord and their relation to motor neuron pathology? 2) Is there neuropathology in other motor control regions in CNS, and what’s their relationship with the spinal cord and how do they contribute to SMA pathology? 3) Do peripheral systems contribute to the SMA pathogenesis? 4) Do current approved treatments eliminate these cellular pathological defects other than rescuing spinal motor neurons and neuromuscular junctions? We hope these kinds of studies will pave the path for a better understanding of SMA pathology and novel treatment strategies. Original research, case report, and review article of submissions are welcomed in this collection.
Topic Editor Dr. Yimin Hua is the Chairman and co-Founder of ASOcura Pharmaceuticals. The other Topic Editors declare no competing conflicts of interest.
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. The SMA field has advanced remarkably since the discovery of the causative survival motor neuron 1(SMN1) gene in 1995. Over the past less than 30 years, intense efforts have elucidated the molecular mechanisms of the SMN gene, which led to the approval of 3 disease-modifying therapies targeting an increase of SMN protein levels since 2016 in the United States. However, none of these high price therapies represents a cure for SMA. There also remain some major limitations and concerns including non-responders, outcome variability, and unknown long-term effects from real-world data. Novel treatment strategies towards the cure of SMA require fully understanding the mechanisms of the SMA pathology.
SMA is widely recognized as a lower motor neurons disease. Hence, most of the 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 may be 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 better and eventually fully understand the mechanisms of SMA pathology, a systematic study of CNS beyond the spinal cord and other systems is crucial.
The aim of this topic is to advocate studies of SMA pathology in all cell types and other motor control regions of CNS in addition to the spinal cord, and the studies in peripheral organs and tissues in both patients and models. For better understanding the mechanisms of SMA pathology, the goal of this collection is to answer key questions, including, but not limited to, 1) What’s the cellular neuropathology of other types of cells including interneurons and glia in the spinal cord and their relation to motor neuron pathology? 2) Is there neuropathology in other motor control regions in CNS, and what’s their relationship with the spinal cord and how do they contribute to SMA pathology? 3) Do peripheral systems contribute to the SMA pathogenesis? 4) Do current approved treatments eliminate these cellular pathological defects other than rescuing spinal motor neurons and neuromuscular junctions? We hope these kinds of studies will pave the path for a better understanding of SMA pathology and novel treatment strategies. Original research, case report, and review article of submissions are welcomed in this collection.
Topic Editor Dr. Yimin Hua is the Chairman and co-Founder of ASOcura Pharmaceuticals. The other Topic Editors declare no competing conflicts of interest.