Article
Biochemistry & Molecular Biology
Francesco Errico, Carmen Marino, Manuela Grimaldi, Tommaso Nuzzo, Valentina Bassareo, Valeria Valsecchi, Chiara Panicucci, Elia Di Schiavi, Tommaso Mazza, Claudio Bruno, Adele D'Amico, Manolo Carta, Anna Maria D'Ursi, Enrico Bertini, Livio Pellizzoni, Alessandro Usiello
Summary: In this study, the metabolic effects of Nusinersen in the cerebrospinal fluid (CSF) of spinal muscular atrophy (SMA) patients were characterized using nuclear magnetic resonance (NMR) spectroscopy. The results showed that Nusinersen can modulate amino acid metabolism with distinct downstream metabolic effects according to disease severity. These findings suggest that Nusinersen selectively modulates peripheral organ metabolism in severe SMA patients.
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
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
Multidisciplinary Sciences
Niko Hensel, Federica Cieri, Pamela Santonicola, Ines Tapken, Tobias Schuening, Michela Taiana, Elisa Pagliari, Antonia Joseph, Silke Fischer, Natascha Heidrich, Hella Brinkmann, Sabrina Kubinski, Anke K. Bergmann, Manuela F. Richter, Klaus Jung, Stefania Corti, Elia Di Schiavi, Peter Claus
Summary: Spinal muscular atrophy (SMA) is a motor neuron disease caused by deletions of the SMN1 gene and low SMN protein levels. Recent studies have identified altered signaling networks in SMA, with two clusters structured around AKT, 14-3-3 zeta/delta, and a major hub connecting both clusters, B-Raf. Down-regulation of B-Raf and 14-3-3 zeta/delta in SMA mice and patients suggests a conserved mechanism across species, with potential therapeutic implications for motoneuron survival.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Claude Cances, Dmitry Vlodavets, Giacomo Pietro Comi, Riccardo Masson, Maria Mazurkiewicz-Beldzinska, Kayoko Saito, Edmar Zanoteli, Angela Dodman, Muna El-Khairi, Ksenija Gorni, Isaac Gravestock, Janine Hoffart, Renata S. Scalco, Basil T. Darras
Summary: The ANCHOVY study findings are consistent with published natural history data on Type 1 SMA, demonstrating the devastating course of the disease, which differs significantly from risdiplam-treated infants. These results provide meaningful additions to the literature, including a broader geographical representation.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Pediatrics
Zhi-Juan Zhong, Pi-Mei Zheng, Hui-Hong Dou, Ji-Gan Wang
Summary: This study aimed to systematically analyze adverse events (AEs) in the treatment of spinal muscular atrophy (SMA) with Nusinersen in children and adolescents. The study found that Nusinersen-related AEs were rare and it effectively reduced common, serious, and fatal AEs in children and adolescents with SMA.
FRONTIERS IN PEDIATRICS
(2023)
Article
Clinical Neurology
Maryam Oskoui, John W. Day, Nicolas Deconinck, Elena S. Mazzone, Andres Nascimento, Kayoko Saito, Carole Vuillerot, Giovanni Baranello, Nathalie Goemans, Janbernd Kirschner, Anna Kostera-Pruszczyk, Laurent Servais, Gergely Papp, Ksenija Gorni, Heidemarie Kletzl, Carmen Martin, Tammy McIver, Renata S. Scalco, Hannah Staunton, Wai Yin Yeung, Paulo Fontoura, Eugenio Mercuri, SUNFISH Working Grp
Summary: Risdiplam, an oral SMN2 pre-mRNA splicing modifier, has been approved for the treatment of SMA. The SUNFISH Part 2 study demonstrated the efficacy and safety of risdiplam in type 2 and non-ambulant type 3 SMA. After 12 months of treatment, motor function improvements were maintained or further improved upon at month 24.
JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Jannik M. Buettner, Leonie Sowoidnich, Florian Gerstner, Beatriz Blanco-Redondo, Stefan Hallermann, Christian M. Simon
Summary: The activation of the p53 pathway is associated with neuronal degeneration in various neurological disorders, including SMA. Aberrant expression of p53 leads to the selective death of motor neurons in SMA. In this study, the expression of p53 downstream targets c-fos, perp, and fas was investigated in vulnerable motor neurons of SMA mice. Nuclear upregulation of c-Fos protein was observed in degenerating motor neurons in different mouse models of SMA, suggesting that it may serve as a readout for therapeutic approaches targeting neuronal death in SMA and other p53-dependent neurodegenerative diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Sharon J. Brown, Rachel A. Kline, Silvia A. Synowsky, Sally L. Shirran, Ian Holt, Kelly A. Sillence, Peter Claus, Brunhilde Wirth, Thomas M. Wishart, Heidi R. Fuller
Summary: This study conducted proteomic profiling of skin fibroblasts from different severities of spinal muscular atrophy (SMA) patients. The results showed limited overlap in differentially expressed proteomic profiles among different types of SMA, and the greatest variability was observed within SMA II fibroblasts. Despite limited proteomic overlap, common enriched canonical pathways were identified in two of the three SMA severities. The study also identified protein profiles that may be associated with SMA severity.
Article
Clinical Neurology
Yu-lian Fang, Na Li, Xiu-fang Zhi, Jie Zheng, Yang Liu, Lin-jie Pu, Chun-yu Gu, Jian-bo Shu, Chun-quan Cai
Summary: This study identified mutations in adjacent genes of the SMN1 gene and other genes that may be associated with the onset of SMA through analysis of SMA family samples, including novel mutations not previously reported.
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Charlotte Spicer, Ching-Hua Lu, Francesco Catapano, Mariacristina Scoto, Irina Zaharieva, Andrea Malaspina, Jennifer E. Morgan, Linda Greensmith, Francesco Muntoni, Haiyan Zhou
Summary: The study found that the levels of neurofilaments in SMA mice and patients can serve as biomarkers for the disease and indicate response to antisense oligonucleotides treatment. However, lower NfH levels in older SMA patients may limit their application as biomarkers. Further research on additional biomarkers for this group of patients is warranted.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Neurosciences
Kathrin Kizina, Yakup Akkaya, Daniel Jokisch, Benjamin Stolte, Andreas Totzeck, Juan Munoz-Rosales, Andreas Thimm, Saskia Bolz, Svenja Brakemeier, Refik Pul, Derya Aslan, Jana Hackert, Christoph Kleinschnitz, Tim Hagenacker
Summary: The cognitive performance of adult SMA patients was evaluated using the WAIS-IV test, which showed that most patients had IQ index scores similar to the normal population, but some SMA type-2 patients had lower scores in working memory and perceptual reasoning. This study further demonstrates that SMA is a multi-systemic disease and challenges the hypothesis that SMA patients may improve cognitive skills to compensate for their physical impairment.
Article
Genetics & Heredity
Anna Lusakowska, Maria Jedrzejowska, Anna Kaminska, Katarzyna Janiszewska, Przemyslaw Grochowski, Janusz Zimowski, Janusz Sierdzinski, Anna Kostera-Pruszczyk
Summary: This study investigates patients included in the Polish Registry of SMA, focusing on the course of type 3 SMA before the availability of disease-modifying treatments. The results show that SMN2 copy number, sex, and age of disease onset strongly affect the age of onset and ambulation in SMA3. Data from this study can provide valuable information for treatment decisions.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Clinical Neurology
Bo Hoon Lee, Megan A. Waldrop, Anne M. Connolly, Emma Ciafaloni
Summary: Newborn screening for SMA and increased genetic carrier screening in 33 US states have led to an increase in early, presymptomatic diagnosis of SMA. Early treatment is crucial for infants with SMA, especially for those who are presymptomatic.
Review
Biochemistry & Molecular Biology
Nora Tula Detering, Tobias Schuening, Niko Hensel, Peter Claus
Summary: Spinal muscular atrophy (SMA) is a disease caused by low levels of survival of motoneuron (SMN) protein. Phosphorylation of SMN is considered a key factor affecting SMN function in SMA. Phosphorylation can influence the localization, stability, and functions of SMN, making it a potential important target in SMA treatment strategies.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Clinical Neurology
Stanley Iyadurai, W. David Arnold, John T. Kissel, Corey Ruhno, Vicki L. McGovern, Pamela J. Snyder, Thomas W. Prior, Jennifer Roggenbuck, Arthur H. Burghes, Stephen J. Kolb
Meeting Abstract
Clinical Neurology
A. Burghes, V. McGovern, C. Ruhno, T. Prior, P. Snyder, J. Roggenbuck, V. Sansone, J. Kissel
NEUROMUSCULAR DISORDERS
(2017)
Article
Biochemistry & Molecular Biology
Chitra C. Iyer, Kaitlyn M. Corlett, Aurelie Massoni-Laporte, Sandra Duque, Narasimhan Madabusi, Sarah Tisdale, Vicki L. McGovern, Thanh T. Le, Phillip G. Zaworski, W. David Arnold, Livio Pellizzoni, Arthur H. M. Burghes
HUMAN MOLECULAR GENETICS
(2018)
Article
Geriatrics & Gerontology
Kajri A. Sheth, Chitra C. Iyer, Christopher G. Wier, Alexander E. Crum, Anna Bratasz, Stephen J. Kolb, Brian C. Clark, Arthur H. M. Burghes, W. David Arnold
NEUROBIOLOGY OF AGING
(2018)
Retraction
Biochemistry & Molecular Biology
Sarmila Majumder, Saradhadevi Varadharaj, Kalpana Ghoshal, Umrao Monani, Arthur H. M. Burghes, Samson T. Jacob
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Genetics & Heredity
Corey Ruhno, Vicki L. McGovern, Matthew R. Avenarius, Pamela J. Snyder, Thomas W. Prior, Flavia C. Nery, Abdurrahman Muhtaseb, Jennifer S. Roggenbuck, John T. Kissel, Valeria A. Sansone, Jennifer J. Siranosian, Alec J. Johnstone, Pann H. Nwe, Ren Z. Zhang, Kathryn J. Swoboda, Arthur H. M. Burghes
Article
Biochemistry & Molecular Biology
Anton J. Blatnik, Vicki L. McGovern, Thanh T. Le, Chitra C. Iyer, Brian K. Kaspar, Arthur H. M. Burghes
HUMAN MOLECULAR GENETICS
(2020)
Article
Biochemistry & Molecular Biology
Vicki L. McGovern, Kaitlyn M. Kray, W. David Arnold, Sandra Duque, Chitra C. Iyer, Aurelie Massoni-Laporte, Eileen Workman, Aalapi Patel, Daniel J. Battle, Arthur H. M. Burghes
HUMAN MOLECULAR GENETICS
(2020)
Article
Geriatrics & Gerontology
Deepti Chugh, Chitra C. Iyer, Prameela Bobbili, Anton J. Blatnik, Brian K. Kaspar, Kathrin Meyer, Arthur H. M. Burghes, Brian C. Clark, W. David Arnold
Summary: The combination of exercise and FST overexpression has positive effects on neuromuscular junction transmission and muscle mass in aging mice, but does not affect motor unit degeneration.
NEUROBIOLOGY OF AGING
(2021)
Article
Geriatrics & Gerontology
Chitra C. Iyer, Deepti Chugh, Prameela J. Bobbili, Anton J. Blatnik, Alexander E. Crum, Allen F. Yi, Brian K. Kaspar, Kathrin C. Meyer, Arthur H. M. Burghes, W. David Arnold
Summary: Research showed that muscle hypertrophy induced by overexpression of follistatin not only increased muscle weight and torque production, but also counteracted age-related degeneration at the neuromuscular junction in mice.
NEUROBIOLOGY OF AGING
(2021)
Article
Biochemistry & Molecular Biology
Anton J. Blatnik, Vicki L. McGovern, Arthur H. M. Burghes
Summary: Proximal spinal muscular atrophy (SMA) is a genetic disorder characterized by motor neuron loss and skeletal muscle atrophy due to deficiency of the essential survival motor neuron (SMN) protein. Therapeutics aimed at increasing SMN protein levels have shown efficacy in treating SMA, but the mechanisms underlying motor neuron loss are still not well understood. Genetics and biochemistry have provided insights into SMA and SMN, from identifying genetic regions to developing potential treatments, but further research is needed to determine critical pathways in SMA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gretchen Thomsen, Arthur H. M. Burghes, Caroline Hsieh, Janet Do, Binh T. T. Chu, Stephanie Perry, Basam Barkho, Petra Kaufmann, Douglas M. Sproule, Douglas E. Feltner, Wendy K. Chung, Vicki L. McGovern, Robert F. Hevner, Miriam Conces, Christopher R. Pierson, Mariacristina Scoto, Francesco Muntoni, Jerry R. Mendell, Kevin D. Foust
Summary: Biodistribution analysis of two patients with spinal muscular atrophy shows widespread onasemnogene abeparvovec DNA, mRNA and SMN protein throughout the central nervous system and peripheral organs following intravenous gene therapy administration. Both patients experienced varying outcomes after receiving the treatment, including improved motor function in one patient and death in the other shortly after administration. The study demonstrates effective distribution, transduction, and expression of onasemnogene abeparvovec throughout the CNS, supporting its potential for restoring SMN expression in individuals with SMA1.
Article
Clinical Neurology
Stephen J. Kolb, Christopher S. Coffey, Jon W. Yankey, Kristin Krosschell, W. David Arnold, Seward B. Rutkove, Kathryn J. Swoboda, Sandra P. Reyna, Ai Sakonju, Basil T. Darras, Richard Shell, Nancy Kuntz, Diana Castro, Julie Parsons, Anne M. Connolly, Claudia A. Chiriboga, Craig McDonald, W. Bryan Burnette, Klaus Werner, Mathula Thangarajh, Perry B. Shieh, Erika Finanger, Merit E. Cudkowicz, Michelle M. McGovern, D. Elizabeth McNeil, Richard Finkel, Susan T. Iannaccone, Edward Kaye, Allison Kingsley, Samantha R. Renusch, Vicki L. McGovern, Xueqian Wang, Phillip G. Zaworski, Thomas W. Prior, Arthur H. M. Burghes, Amy Bartlett, John T. Kissel
ANNALS OF NEUROLOGY
(2017)