Article
Medicine, Research & Experimental
Audrey M. Winkelsas, Christopher Grunseich, George G. Harmison, Katarzyna Chwalenia, Carlo Rinaldi, Suzan M. Hammond, Kory Johnson, Melissa Bowerman, Sukrat Arya, Kevin Talbot, Matthew J. Wood, Kenneth H. Fischbeck
Summary: Research shows that ASOs targeting the 50 end of SMN2 can increase SMN mRNA and protein levels by inhibiting SMN2 mRNA decay. Combining 50 UTR ASO with SSO can elevate SMN levels beyond those achieved with SSO alone, offering a new therapeutic target for SMA.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Medical Laboratory Technology
Weijiang Jin, Zhengquan Yang, Xiaojun Tang, Xiuchao Wang, Yaxin Huang, Chenmin Hui, Jiaming Yao, Ju Luan, Shaohua Tang, Shengnan Wu, Shengnan Jin, Chunming Ding
Summary: This study reports the MS-CNV method for the quantification of SMN1 and SMN2 gene dosages in spinal muscular atrophy (SMA). The method is accurate and high-throughput, and can be used for carrier screening and genetic diagnosis of SMA.
CLINICA CHIMICA ACTA
(2022)
Review
Biology
Andres Lopez-Cortes, Gabriela Echeverria-Garces, Maria Jose Ramos-Medina
Summary: 5q spinal muscular atrophy is a common pediatric recessive genetic disease, and there have been significant advancements in its treatment. Promising data from early-stage clinical trials suggest that more therapeutic options may be available in the future.
Review
Biochemistry & Molecular Biology
Eleonora Zilio, Valentina Piano, Brunhilde Wirth
Summary: This review discusses the impact of spinal muscular atrophy (SMA) on mitochondrial functions in the neuronal and muscular systems, highlighting the potential contribution of mitochondrial defects to disease progression and the potential of restoring mitochondrial functionality as a therapeutic approach. The study also provides a list of transcripts encoding mitochondrial proteins affected in various SMA models and speculates that age-related mitochondrial deterioration may play a crucial role in adult SMA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Hisahide Nishio, Kentaro Okamoto, Hiroyuki Awano, Toshio Saito, Yasuhiro Takeshima, Masakazu Shinohara
Summary: This study examined the effects of high-concentration ASOs and combining two ASOs on splicing efficiency using SMA fibroblasts. The results showed that low or intermediate concentrations of ASOs had better splicing efficiency, while high concentrations of ASOs resulted in the creation of a cryptic exon.
Article
Clinical Neurology
Astrid Pechmann, Max Behrens, Katharina Doernbrack, Adrian Tassoni, Sabine Stein, Sibylle Vogt, Daniela Zoeller, Gunther Bernert, Tim Hagenacker, Ulrike Schara-Schmidt, Inge Schwersenz, Maggie C. Walter, Matthias Baumann, Manuela Baumgartner, Marcus Deschauer, Astrid Eisenkoelbl, Marina Flotats-Bastardas, Andreas Hahn, Veronka Horber, Ralf A. Husain, Sabine Illsinger, Jessika Johannsen, Cornelia Koehler, Heike Koelbel, Monika Mueller, Arpad von Moers, Kurt Schlachter, Gudrun Schreiber, Oliver Schwartz, Martin Smitka, Elisabeth Steiner, Eva Stoegmann, Regina Trollmann, Katharina Vill, Claudia Weiss, Gert Wiegand, Andreas Ziegler, Hanns Lochmueller, Janbernd Kirschner
Summary: This study presents real-world evidence on the effects of nusinersen treatment in patients with early-onset spinal muscular atrophy. The findings demonstrate significant improvements in motor function, particularly in children under the age of 2. However, the improvements in bulbar and respiratory function are not equivalent to those in motor function.
Article
Biochemistry & Molecular Biology
Laura Blasco-Perez, Mar Costa-Roger, Jordi Leno-Colorado, Sara Bernal, Laura Alias, Marta Codina-Sola, Desiree Martinez-Cruz, Claudia Castiglioni, Enrico Bertini, Lorena Travaglini, Jose M. Millan, Elena Aller, Javier Sotoca, Raul Juntas, Christina Engel Hoei-Hansen, Antonio Moreno-Escribano, Encarna Guillen-Navarro, Laura Costa-Comellas, Francina Munell, Susana Boronat, Ricardo Rojas-Garcia, Monica Povedano, Ivon Cusco, Eduardo F. Tizzano
Summary: This study provides a deep molecular characterization of SMN2 in SMA patients, highlighting the importance of the c.859G>C variant as a modifier and the need to accurately assess the entire SMN2 region for improving prognostic outcomes and understanding complex genotype-phenotype correlations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Review
Biochemistry & Molecular Biology
Hisahide Nishio, Emma Tabe Eko Niba, Toshio Saito, Kentaro Okamoto, Yasuhiro Takeshima, Hiroyuki Awano
Summary: Spinal muscular atrophy (SMA) is an autosomal recessive lower motor neuron disease. The genetic homogeneity of SMA was proved in 1990, five years after the identification of the responsible gene, SMN1. Genetic testing has revealed that SMA occurs in 1 of 10,000 to 20,000 live births and more than 95% of affected patients have SMN1 deletion. Nusinersen, onasemnogene abeparvovec, and risdiplam have been approved for SMA treatment, and clinical trials have shown that pre-symptomatic SMA patients can achieve developmental milestones with these drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Matthew E. R. Butchbach
Summary: Spinal muscular atrophy (SMA) is a genetic disease characterized by loss of spinal motor neurons leading to muscle weakness and atrophy. Current therapeutic options for SMA focus on increasing SMN2 expression to increase the amount of SMN protein. Genetic heterogeneity in SMN genes can impact disease phenotype and treatment efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Marianna Maretina, Anna Egorova, Kristina Lanko, Vladislav Baranov, Anton Kiselev
Summary: This study tested three methods for measuring SMN transcript levels and compared several potential mRNA-based biomarkers in peripheral blood mononuclear cells of SMA patients, SMA carriers, and healthy individuals. The study found that the mean percentage of full-length SMN transcripts determined by semiquantitative and quantitative fluorescence RT-PCR differed significantly between the groups. The relevance of this biomarker was confirmed in a therapeutic experiment targeting the SMN2 gene.
Article
Medicine, General & Internal
Sally Dunaway Young, Jacqueline Montes, Allan M. Glanzman, Richard Gee, John W. Day, Richard S. Finkel, Basil T. Darras, Darryl C. De Vivo, Giulia Gambino, Richard Foster, Janice Wong, Steve Garafalo, Zdenek Berger
Summary: Nusinersen treatment can improve or stabilize motor function in non-ambulatory children with later-onset spinal muscular atrophy (SMA). The severity of baseline scoliosis is associated with later motor function, with greater decline in motor function observed in children with more severe scoliosis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Marina Boido, Iacopo Gesmundo, Anna Caretto, Francesca Pedrolli, Roberta Schellino, Sheila Leone, Renzhi Cai, Wei Sha, Ezio Ghigo, Andrew V. Schally, Alessandro Vercelli, Riccarda Granata
Summary: The study shows that MR-409 has protective effects on SMN Delta 7 mice, indicating its potential as a promising drug for the treatment of SMA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Pharmacology & Pharmacy
Giovanni Baranello, Ksenija Gorni, Monica Daigl, Anna Kotzeva, Rachel Evans, Neil Hawkins, David A. Scott, Anadi Mahajan, Francesco Muntoni, Laurent Servais
Summary: Spinal muscular atrophy (SMA) is a rare neuromuscular disease with different types, and various factors influence the prognosis of patients, with early diagnosis and treatment being crucial for type 1 SMA, while type 2 and 3 patients need to pay attention to changes in motor function and the risk of complications.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Neurosciences
Robert M. Brownstone, Camille Lancelin
JOURNAL OF NEUROPHYSIOLOGY
(2018)
Article
Multidisciplinary Sciences
Delphine Sapaly, Matthieu Dos Santos, Perrine Delers, Olivier Biondi, Gwendoline Querol, Leo Houdebine, Kevinee Khoobarry, Francois Girardet, Philippe Burlet, Anne-Sophie Armand, Christophe Chanoine, Jean-Francois Bureau, Frederic Charbonnier, Suzie Lefebvre
SCIENTIFIC REPORTS
(2018)
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
Developmental Biology
Bruno Della Gaspera, Alice Mateus, Yannick Andeol, Laure Weill, Frederic Charbonnier, Christophe Chanoine
DEVELOPMENTAL BIOLOGY
(2019)
Article
Neurosciences
Laia Just-Borras, Erica Hurtado, Victor Cilleros-Mane, Olivier Biondi, Frederic Charbonnier, Marta Tomas, Neus Garcia, Maria A. Lanuza, Josep Tomas
MOLECULAR NEUROBIOLOGY
(2019)
Article
Physiology
Leeo Houdebine, Domenico D'Amico, Jean Bastin, Farah Chali, Celine Desseille, Valentin Rumeau, Judy Soukkari, Carole Oudot, Thais Rouquet, Bruno Bariohay, Julien Roux, Delphine Sapaly, Laure Weill, Philippe Lopes, Fatima Djouadi, Cynthia Bezier, Frederic Charbonnier, Olivier Biondi
FRONTIERS IN PHYSIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Laia Just-Borras, Erica Hurtado, Victor Cilleros-Mane, Olivier Biondi, Frederic Charbonnier, Marta Tomas, Neus Garcia, Josep Tomas, Maria A. Lanuza
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Laia Just-Borras, Victor Cilleros-Mane, Erica Hurtado, Olivier Biondi, Frederic Charbonnier, Marta Tomas, Neus Garcia, Josep Tomas, Maria A. Lanuza
Summary: Physical exercise improves motor control, cognitive abilities, and neuroprotection in the nervous system. Studies show that exercise can induce molecular adaptations in muscles, transitioning them towards a slower, more resistant phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Remi Ronzano, Camille Lancelin, Gardave Singh Bhumbra, Robert M. Brownstone, Marco Beato
Summary: The study reveals that premotor neurons in the spinal cord have divergent projections to synergist or antagonist muscle MNs, indicating coordination of activity across multiple motor pools. Additionally, spinal neurons mediating co-contraction of antagonist muscles were identified, shedding light on the potential mechanisms behind muscle coordination and potential implications for neurological diseases like dystonia.
Article
Psychiatry
Maria Goldberg, Md Rezaul Islam, Cemil Kerimoglu, Camille Lancelin, Verena Gisa, Susanne Burkhardt, Dennis M. Krueger, Till Marquardt, Berend Malchow, Andrea Schmitt, Peter Falkai, Farahnaz Sananbenesi, Andre Fischer
Summary: Exercise can enhance memory function in healthy humans, with a cluster of 18 microRNAs highly correlated to cognition, among which microRNA-409-5p and microRNA-501-3p are the most significantly regulated candidates, playing crucial roles in neuronal integrity, synaptic plasticity, and morphology.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Cell Biology
Bruno Della Gaspera, Laure Weill, Christophe Chanoine
Summary: This article summarizes the literature on somite compartmentalization and proposes a model for the evolutionary history of somite compartmentalization. The study suggests that somites in vertebrates have evolved through two major transitions, involving changes in the cell potency of somitic cells and the formation of different vertebrate compartments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Clinical Neurology
Domenico D'Amico, Olivier Biondi, Camille Januel, Cynthia Bezier, Delphine Sapaly, Zoe Clerc, Mirella El Khoury, Venkat Krishnan Sundaram, Leo Houdebine, Thibaut Josse, Bruno Della Gaspera, Cecile Martinat, Charbel Massaad, Laure Weill, Frederic Charbonnier
Summary: This study reveals that the IRE1 alpha/XBP1 branch of the unfolded protein response is disrupted in spinal muscular atrophy (SMA), with a depletion of XBP1s contributing to SMA pathogenesis. Rebalancing XBP1s expression can induce SMN expression and protect spinal motor neurons in severe SMA-like mice.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mudassar N. Khan, Pitchaiah Cherukuri, Francesco Negro, Ashish Rajput, Piotr Fabrowski, Vikas Bansal, Camille Lancelin, Tsung- Lee, Yehan Bian, William P. Mayer, Turgay Akay, Daniel Mueller, Stefan Bonn, Dario Farina, Till Marquardt
Summary: The ability of terrestrial vertebrates to effectively move on land is closely related to the diversification of motor neurons. Recent studies have identified gene expression signatures linked to both motor neuron types. Loss of orphan nuclear receptors ERR2 and ERR3 disrupts the functional properties and precision movements of gamma motor neurons.
Article
Biology
Remi Ronzano, Sophie Skarlatou, Bianca K. Barriga, B. Anne Bannatyne, Gardave Singh Bhumbra, Joshua D. Foster, Jeffrey D. Moore, Camille Lancelin, Amanda M. Pocratsky, Mustafa Goerkem Ozyurt, Calvin Chad Smith, Andrew J. Todd, David J. Maxwell, Andrew J. Murray, Samuel L. Pfaff, Robert M. Brownstone, Niccolo Zampieri, Marco Beato
Summary: In this study, multiple viral-tracing methods were used to investigate the organization of premotor interneurons contacting motor pools controlling flexion and extension of the ankle. Contrary to expectations, it was found that these premotor interneurons are highly intermingled with motor neurons, suggesting the absence of clear spatial patterns in the processing of motor instructions.