Article
Neurosciences
Christian M. Simon, Beatriz Blanco-Redondo, Jannik M. Buettner, John G. Pagiazitis, Emily V. Fletcher, Josiane K. Sime Longang, George Z. Mentis
Summary: The study reveals that chronic treatment with 4-aminopyridine (4-AP) improves motor behavior in both sexes of a severe mouse model of spinal muscular atrophy (SMA) by increasing neuronal activity, restoring neurotransmission and synapse numbers, particularly proprioceptive synapses and neuromuscular junctions (NMJs), without affecting motor neuron death. Additionally, combining 4-AP treatment with pharmacological inhibition of p53-dependent motor neuron death leads to additive effects, fully correcting sensory-motor circuit pathology and enhancing phenotypic benefits in SMA mice.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Giulietta M. M. Riboldi, Irene Faravelli, Paola Rinchetti, Francesco Lotti
Summary: Since its identification as the gene responsible for SMA, the functions of the SMN protein have expanded to include roles in RNA processing pathways, mRNA trafficking and translation, axonal transport, endocytosis, and mitochondria metabolism. The SMN complex's activities are regulated by various processes, with post-translational modifications (PTMs) emerging as important regulators. PTMs, such as phosphorylation, methylation, ubiquitination, acetylation, and sumoylation, modulate the pleiotropic functions of the SMN complex. This overview focuses on the PTMs involved in regulating the SMN complex and their implications in SMA pathogenesis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Mandana Arbab, Zaneta Matuszek, Kaitlyn M. Kray, Ailing Du, Gregory A. Newby, Anton J. Blatnik, Aditya Raguram, Michelle F. Richter, Kevin T. Zhao, Jonathan M. Levy, Max W. Shen, W. David Arnold, Dan Wang, Jun Xie, Guangping Gao, Arthur H. M. Burghes, David R. Liu
Summary: Spinal muscular atrophy (SMA), a leading genetic cause of infant mortality, can be treated by genome editing of SMN2 to restore SMN protein levels and rescue SMA phenotypes, demonstrating the potential of a one-time base editing treatment for SMA.
Article
Neurosciences
Emily J. Reedich, Martin Kalski, Nicholas Armijo, Gregory A. Cox, Christine J. DiDonato
Summary: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by genetic deficiency of the SMN protein. Studies have shown activation of the p53 and p21 pathways in SMA mice, but they are not primary drivers of motor neuron death in milder SMA mouse models like Smn(2B/-).
EXPERIMENTAL NEUROLOGY
(2021)
Article
Clinical Neurology
P. V. S. Souza, W. B. V. R. Pinto, A. Ricarte, B. M. L. Badia, D. D. Seneor, D. T. Teixeira, L. Caetano, E. A. Goncalves, M. A. T. Chieia, I. B. Farias, E. Bertini, A. S. B. Oliveira
Summary: This study identified a cohort of 20 patients with SMA type 4 in a Brazilian cohort of 227 SMA patients. The most common clinical symptom was limb-girdle muscle weakness, with absent tendon reflexes in 90% of patients and fasciculations in 45% of patients. The majority of patients (80%) had the homozygous deletion of exon 7 in the SMN1 gene, with 60% of them showing four copies of the SMN2 gene.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Rachel James, Helena Chaytow, Leire M. Ledahawsky, Thomas H. Gillingwater
Summary: SMA is an autosomal recessive motor neuron disease caused by mutations in the SMN1 gene. The development of combinatorial therapies for SMA is necessary, with mitochondria being a relevant target for such therapies. Understanding mitochondrial dysfunction in SMA may lead to the development of targeted mitochondrial therapies with potential benefits for other motor neuron diseases and neurodegenerative disorders.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Raffaella Adami, Daniele Bottai
Summary: Studying neural stem cells (NSCs) from spinal muscular atrophy (SMA) patients is important for identifying new treatment targets and supporting affected patients. However, studying NSCs in living patients is challenging, but can be done using animal models or induced pluripotent stem cells. Therapeutic interventions like NSCs transplantation could improve SMA condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Chaoping Hu, Xihua Li, Yiyun Shi, Xiaomei Zhu, Lei Zhao, Wenhui Li, Shuizhen Zhou, Yi Wang
Summary: This study provides insight into the comprehensive management and profile of different types of SMA patients in China, highlighting the importance of higher SMN2 copies for better survival and ambulation preservation. Patients receiving regular rehabilitation may have better joint function preservation.
FRONTIERS IN NEUROLOGY
(2022)
Review
Cell Biology
Kishore Gollapalli, Jeong-Ki Kim, Umrao R. Monani
Summary: Infantile-onset spinal muscular atrophy is a neurodegenerative disease caused by a housekeeping protein dysfunction. Research is ongoing to understand why this happens and whether other cell types contribute to the disease. New findings, while sometimes puzzling, advocate for a careful re-examination of study outcomes and emphasize the importance of mild models in identifying key mechanisms driving neuromuscular dysfunction in the disease.
NEURAL REGENERATION RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Mar Costa-Roger, Laura Blasco-Perez, Ivon Cusco, Eduardo F. Tizzano
Summary: Comprehensive study of the SMN1 and SMN2 genes is crucial for better prediction of SMA in positive neonatal screening cases and early diagnosis to start treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Ayse Yesbek Kaymaz, Sevgi Kostel Bal, Gamze Bora, Beril Talim, Alev Ozon, Ayfer Alikasifoglu, Haluk Topaloglu, Hayat Erdem Yurter
Summary: In this study, the components of the IGF-I system in serum and skeletal muscle biopsies of spinal muscular atrophy (SMA) patients were analyzed. The results showed a decrease in IGF-I levels and an increase in IGFBP-5 levels in the serum of SMA patients compared to healthy controls. Increased expression of IGF-I, IGF-I receptor, and IGFBP-5 was detected in skeletal muscle biopsies of SMA patients. These findings suggest alterations in the IGF-I system at both the systemic and tissue-specific levels in SMA patients.
Article
Clinical Neurology
Andrea Barp, Elena Carraro, Francesca Salmin, Andrea Lizio, Marta Cheli, Valeria Sansone
Summary: This study explored facial nerve response, MUNIX, and MUSIX in patients with spinal muscular atrophy (SMA) and compared them with healthy control subjects. The results showed that CMAP of the facial nerve and MUNIX of the orbicularis oculi muscle had high accuracy in discriminating between different subtypes of SMA and quantifying motor unit loss of the facial nerve.
Review
Pharmacology & Pharmacy
Charlotte A. Rene, Robin J. Parks
Summary: Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the SMN1 gene, leading to reduced SMN protein levels. SMA patients experience loss of alpha motor neurons in the spinal cord, resulting in skeletal muscle atrophy and other tissue and organ deficits. Onasemnogene abeparvovec, an AAV-based gene therapy, has shown promising results in treating infants and young children with SMA.
Review
Pediatrics
John W. Day, Kelly Howell, Amy Place, Kimberly Long, Jose Rossello, Nathalie Kertesz, George Nomikos
Summary: Spinal muscular atrophy (SMA) is a genetic neuromuscular condition that affects spinal motor neurons. Current treatments have provided incremental improvements, but there is still a significant disease burden for many patients. The development of a combination therapy targeting myostatin inhibition shows potential for managing SMA.
Review
Medicine, General & Internal
Marija Babic, Maria Banovic, Ivana Berecic, Tea Banic, Mirjana Babic Leko, Monika Ulamec, Alisa Junakovic, Janja Kopic, Jadranka Sertic, Nina Barisic, Goran Simic
Summary: Spinal muscular atrophy (SMA) is a rare genetic disorder caused by the deletion or mutation of the SMN1 gene. Nusinersen and risdiplam, the first FDA-approved medications, increase the production of SMN protein from the backup SMN2 gene. The search for prognostic and pharmacodynamic biomarkers in SMA patients' body fluids is ongoing, although more research is needed to identify new biomarkers or combinations of biomarkers.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Neurosciences
Olivier Biondi, Julien Branchu, Amina Ben Salah, Leo Houdebine, Lise Bertin, Farah Chali, Celine Desseille, Laure Weill, Gabriel Sanchez, Camille Lancelin, Saba Aid, Philippe Lopes, Claude Pariset, Sylvie Lecolle, Jocelyn Cote, Martin Holzenberger, Christophe Chanoine, Charbel Massaad, Frederic Charbonnier
JOURNAL OF NEUROSCIENCE
(2015)
Review
Genetics & Heredity
Alan Morettin, R. Mitchell Baldwin, Jocelyn Cote
Article
Biochemistry & Molecular Biology
Gabriel Sanchez, Emma Bondy-Chorney, Janik Laframboise, Genevieve Paris, Andreanne Didillon, Bernard J. Jasmin, Jocelyn Cote
NUCLEIC ACIDS RESEARCH
(2016)
Article
Cell Biology
Aymeric Ravel-Chapuis, Amanda Klein Gunnewiek, Guy Belanger, Tara E. Crawford Parks, Jocelyn Cote, Bernard J. Jasmin
MOLECULAR BIOLOGY OF THE CELL
(2016)
Article
Genetics & Heredity
Emma Bondy-Chorney, Tara E. Crawford Parks, Aymeric Ravel-Chapuis, Roscoe Klinck, Lynda Rocheleau, Martin Pelchat, Benoit Chabot, Bernard J. Jasmin, Jocelyn Cote
Article
Biochemistry & Molecular Biology
Tara E. Crawford Parks, Aymeric Ravel-Chapuis, Emma Bondy-Chorney, Jean-Marc Renaud, Jocelyn Cote, Bernard J. Jasmin
HUMAN MOLECULAR GENETICS
(2017)
Article
Biochemistry & Molecular Biology
Aymeric Ravel-Chapuis, Guy Belanger, Jocelyn Cote, Robin N. Michel, Bernard J. Jasmin
HUMAN MOLECULAR GENETICS
(2017)
Article
Biochemistry & Molecular Biology
Emma Bondy-Chorney, R. Mitchell Baldwin, Andreanne Didillon, Benoit Chabot, Bernard J. Jasmin, Jocelyn Cote
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2017)
Article
Multidisciplinary Sciences
Alan Morettin, Genevieve Paris, Younes Bouzid, R. Mitchell Baldwin, Theresa J. Falls, John C. Bell, Jocelyn Cote
SCIENTIFIC REPORTS
(2017)
Article
Genetics & Heredity
Meaghen Rollins, Sylvain Huard, Alan Morettin, Jennifer Takuski, Trang Thuy Pham, Morgan D. Fullerton, Jocelyn Cote, Kristin Baetz
Article
Multidisciplinary Sciences
Maneka Chitiprolu, Chantal Jagow, Veronique Tremblay, Emma Bondy-Chorney, Genevieve Paris, Alexandre Savard, Gareth Palidwor, Francesca A. Barry, Lorne Zinman, Julia Keith, Ekaterina Rogaeva, Janice Robertson, Mathieu Lavallee-Adam, John Woulfe, Jean-Francois Couture, Jocelyn Cote, Derrick Gibbings
NATURE COMMUNICATIONS
(2018)
Article
Multidisciplinary Sciences
Tara E. Crawford Parks, Kristen A. Marcellus, Jonathan Langill, Aymeric Ravel-Chapuis, Jean Michaud, Kyle N. Cowan, Jocelyn Cote, Bernard J. Jasmin
SCIENTIFIC REPORTS
(2017)
Article
Cell Biology
Nasim Haghandish, R. Mitchell Baldwin, Alan Morettin, Haben Tesfu Dawit, Hemanta Adhikary, Jean-Yves Masson, Rachid Mazroui, Laura Trinkle-Mulcahy, Jocelyn Cote
MOLECULAR BIOLOGY OF THE CELL
(2019)
Article
Cell Biology
Huishan Guo, Maneka Chitiprolu, Luc Roncevic, Charlotte Javalet, Fiona J. Hemming, My Tran Trung, Lingrui Meng, Elyse Latreille, Christiano Tanese de Souza, Danielle McCulloch, R. Mitchell Baldwin, Rebecca Auer, Jocelyn Cote, Ryan Charles Russell, Remy Sadoul, Derrick Gibbings
DEVELOPMENTAL CELL
(2017)
Article
Medicine, Research & Experimental
Emma Bondy-Chorney, Tara E. Crawford Parks, Aymeric Ravel-Chapuis, Bernard J. Jasmin, Jocelyn Cote