Therapeutic strategies for the treatment of spinal muscular atrophy

2012 ◽  
Vol 4 (13) ◽  
pp. 1733-1750 ◽  
Author(s):  
Jonathan J Cherry ◽  
Elliot J Androphy
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Therapeutic Strategies

Spinal muscular atrophy: state of the art and new therapeutic strategies

2021 ◽  
Author(s):  
Sonia Messina ◽  
Maria Sframeli ◽  
Lorenzo Maggi ◽  
Adele D’Amico ◽  
Claudio Bruno ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
State Of The Art ◽  
Muscular Atrophy ◽  
Therapeutic Strategies

scholarly journals Therapeutic strategies for spinal muscular atrophy: SMN and beyond

2017 ◽  
Vol 10 (8) ◽  
pp. 943-954 ◽  
Author(s):  
Melissa Bowerman ◽  
Catherina G. Becker ◽  
Rafael J. Yáñez-Muñoz ◽  
Ke Ning ◽  
Matthew J. A. Wood ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Therapeutic Strategies

Therapeutic Strategies for the Treatment of Spinal Muscular Atrophy (SMA) Disease

2006 ◽  
Vol 7 (6) ◽  
pp. 381-386 ◽  
Author(s):  
Federica Sangiuolo ◽  
Annalisa Botta ◽  
Antonio Filareto ◽  
Paola Spitalieri ◽  
Giuseppe Novelli
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Therapeutic Strategies

Therapeutic targets for spinal muscular atrophy : Inhibiting the inhibitors

2014 ◽  
Author(s):  
◽  
Erkan Y. Osman
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Complex Disease ◽  
Muscular Atrophy ◽  
Autosomal Recessive Disorder ◽  
Therapeutic Strategies ◽  
Cellular Level ◽  
Survival Motor Neuron ◽  
Clinical Consequence ◽  
University Of Missouri

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Spinal muscular atrophy (SMA) is an autosomal recessive disorder that is a leading genetic cause of infantile death. SMA is the most common inherited motor neuron disease and occurs in approximately 1: 6,000 live births. The gene responsible for SMA is called survival motor neuron-1 (SMN1). A human-specific copy gene is present on the same region of chromosome 5q called SMN2. SMN2 is nearly identical to SMN1; however, mutations in SMN2 have no clinical consequence if SMN1 is retained. The reason why SMN2 cannot prevent disease development in the absence of SMN1 is that the majority of SMN2-derived transcripts are alternatively spliced, resulting in a truncated and unstable protein. The presence of SMN2 in all SMA patients is fundamental to the biology of the disease; however, from a translational perspective, targeting SMN2 may prove to be the most important therapeutic opportunity for all patients. The presence of SMN2 opens the door to a number of exciting therapeutic strategies, including anti-sense oligonucleotides (ASOs) that prevent the pathogenic SMN2 splicing event. Our efforts are focused on several repressor regions upstream and downstream of SMN2 exon 7. Importantly, when manipulating these repressor regions, hallmarks of the disease at the cellular level such as neuromuscular junction pathology in various SMA animal models are corrected. Currently, there are no approved SMA-specific compounds, and developing a broad array of therapeutic strategies to address this complex disease is essential. The development and design of highly-potent ASOs provide novel molecular targets for SMA therapeutics that can dramatically improve disease phenotype and extend patients' life span.

scholarly journals Molecular, genetic and stem cell‐mediated therapeutic strategies for spinal muscular atrophy ( SMA )

2014 ◽  
Vol 18 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Chiara Zanetta ◽  
Giulietta Riboldi ◽  
Monica Nizzardo ◽  
Chiara Simone ◽  
Irene Faravelli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Molecular Genetic ◽  
Therapeutic Strategies

scholarly journals Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Antoine Cléry ◽  
Miroslav Krepl ◽  
Cristina K. X. Nguyen ◽  
Ahmed Moursy ◽  
Hadi Jorjani ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Binding Site ◽  
Mode Of Action ◽  
Solution Structure ◽  
Muscular Atrophy ◽  
Rna Metabolism ◽  
Therapeutic Strategies ◽  
Pivotal Role ◽  
Sr Protein ◽  
New Perspective

AbstractThe human prototypical SR protein SRSF1 is an oncoprotein that contains two RRMs and plays a pivotal role in RNA metabolism. We determined the structure of the RRM1 bound to RNA and found that the domain binds preferentially to a CN motif (N is for any nucleotide). Based on this solution structure, we engineered a protein containing a single glutamate to asparagine mutation (E87N), which gains the ability to bind to uridines and thereby activates SMN exon7 inclusion, a strategy that is used to cure spinal muscular atrophy. Finally, we revealed that the flexible inter-RRM linker of SRSF1 allows RRM1 to bind RNA on both sides of RRM2 binding site. Besides revealing an unexpected bimodal mode of interaction of SRSF1 with RNA, which will be of interest to design new therapeutic strategies, this study brings a new perspective on the mode of action of SRSF1 in cells.

scholarly journals Spinal muscular atrophy: from tissue specificity to therapeutic strategies

2015 ◽  
Vol 7 ◽  
Author(s):  
Daniel M. Iascone ◽  
Christopher E. Henderson ◽  
Justin C. Lee
Keyword(s):  
Spinal Muscular Atrophy ◽  
Tissue Specificity ◽  
Muscular Atrophy ◽  
Therapeutic Strategies
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