Next Article in Journal
The Enticing Path of miR Therapeutics: Difficult but Not without Prospects
Previous Article in Journal
Cytoskeletal Protein Variants Driving Atrial Fibrillation: Potential Mechanisms of Action
Review

Restoring SMN Expression: An Overview of the Therapeutic Developments for the Treatment of Spinal Muscular Atrophy

by 1 and 1,2,3,*
1
Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, 116 St. and 85 Ave., Edmonton, AB T6G 2E1, Canada
2
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, 116 St. and 85 Ave., Edmonton, AB T6G 2E1, Canada
3
The Friends of Garret Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, 8812 112 St., Edmonton, AB T6G 2H7, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Cédric Raoul
Cells 2022, 11(3), 417; https://doi.org/10.3390/cells11030417
Received: 20 December 2021 / Revised: 14 January 2022 / Accepted: 24 January 2022 / Published: 26 January 2022
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder and one of the most common genetic causes of infant death. It is characterized by progressive weakness of the muscles, loss of ambulation, and death from respiratory complications. SMA is caused by the homozygous deletion or mutations in the survival of the motor neuron 1 (SMN1) gene. Humans, however, have a nearly identical copy of SMN1 known as the SMN2 gene. The severity of the disease correlates inversely with the number of SMN2 copies present. SMN2 cannot completely compensate for the loss of SMN1 in SMA patients because it can produce only a fraction of functional SMN protein. SMN protein is ubiquitously expressed in the body and has a variety of roles ranging from assembling the spliceosomal machinery, autophagy, RNA metabolism, signal transduction, cellular homeostasis, DNA repair, and recombination. Motor neurons in the anterior horn of the spinal cord are extremely susceptible to the loss of SMN protein, with the reason still being unclear. Due to the ability of the SMN2 gene to produce small amounts of functional SMN, two FDA-approved treatment strategies, including an antisense oligonucleotide (AON) nusinersen and small-molecule risdiplam, target SMN2 to produce more functional SMN. On the other hand, Onasemnogene abeparvovec (brand name Zolgensma) is an FDA-approved adeno-associated vector 9-mediated gene replacement therapy that can deliver a copy of the human SMN1. In this review, we summarize the SMA etiology, the role of SMN, and discuss the challenges of the therapies that are approved for SMA treatment. View Full-Text
Keywords: spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (AON); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (AON); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule
Show Figures

Graphical abstract

MDPI and ACS Style

Aslesh, T.; Yokota, T. Restoring SMN Expression: An Overview of the Therapeutic Developments for the Treatment of Spinal Muscular Atrophy. Cells 2022, 11, 417. https://doi.org/10.3390/cells11030417

AMA Style

Aslesh T, Yokota T. Restoring SMN Expression: An Overview of the Therapeutic Developments for the Treatment of Spinal Muscular Atrophy. Cells. 2022; 11(3):417. https://doi.org/10.3390/cells11030417

Chicago/Turabian Style

Aslesh, Tejal, and Toshifumi Yokota. 2022. "Restoring SMN Expression: An Overview of the Therapeutic Developments for the Treatment of Spinal Muscular Atrophy" Cells 11, no. 3: 417. https://doi.org/10.3390/cells11030417

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop