Article
Medicine, General & Internal
Wiebke Hermann, Simona Langner, Maren Freigang, Stefanie Fischer, Alexander Storch, Rene Guenther, Andreas Hermann
Summary: Respiratory dysfunction is a common complication in motor neuron disease patients, and traditional measures of respiratory function are limited in these patients. This study suggests that diaphragm ultrasound imaging may be a useful tool for evaluating respiratory dysfunction in adult patients with motor neuron disease.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biotechnology & Applied Microbiology
Defne A. Amado, Beverly L. Davidson
Summary: ALS has historically been challenging for gene therapy due to a lack of therapeutic targets and difficulty accessing the brain and spinal cord. Recent advances in disease mechanism understanding, ALS genetics, and CNS targeting, along with progress in gene delivery and editing techniques, have opened new therapeutic possibilities. Gene therapy clinical trials are underway for ALS patients with various genetic mutations, showing potential for disease-modifying treatment.
Article
Biochemistry & Molecular Biology
Claudia Malacarne, Mariarita Galbiati, Eleonora Giagnorio, Paola Cavalcante, Franco Salerno, Francesca Andreetta, Cinza Cagnoli, Michela Taiana, Monica Nizzardo, Stefania Corti, Viviana Pensato, Anna Venerando, Cinzia Gellera, Silvia Fenu, Davide Pareyson, Riccardo Masson, Lorenzo Maggi, Eleonora Dalla Bella, Giuseppe Lauria, Renato Mantegazza, Pia Bernasconi, Angelo Poletti, Silvia Bonanno, Stefania Marcuzzo
Summary: Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. Recent research has highlighted the potential role of myomiRs as promising biomarkers in MNDs, with dysregulation of these molecules observed in both mouse models and human patients. Further investigation is needed to explore the therapeutic potential of myomiRs in MND treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Xinmei Wen, Wenjia Zhu, Nan L. Xia, Qianwen Li, Li Di, Shu Zhang, Hai Chen, Yan Lu, Min Wang, Min Xu, Suobin Wang, Xin-Ming Shen, Jie Lu, Yuwei Da
Summary: Amyotrophic lateral sclerosis (ALS) is a common motor neuron disease with diverse clinical presentations and genetic causes. Different missense mutations in the SOD1 gene have been identified to cause familial ALS, and a novel mutation may lead to fast-deteriorating pure lower motor neuron symptoms. Modeling of all R116 substitutions in the SOD1 protein structure showed a shared mechanism of destroyed hydrogen bonds, potentially resulting in neurotoxicity.
FRONTIERS IN GENETICS
(2021)
Article
Clinical Neurology
Tyler R. R. Fortuna, Sukhleen Kour, Anuradha Venkatakrishnan Chimata, Anixa Muinos-Buehl, Eric N. N. Anderson, Charlie H. H. Nelson IV, Caroline Ward, Om Chauhan, Casey O'Brien, Dhivyaa Rajasundaram, Deepa S. S. Rajan, Brunhilde Wirth, Amit Singh, Udai Bhan Pandey
Summary: GEMIN5 is essential for the assembly of snRNPs and its dysfunction is associated with neurodevelopmental disorders. This study reveals that SMN acts as a genetic suppressor of GEMIN5-mediated neurodegeneration by enhancing GEMIN5 expression. The expression patterns of SMN and GEMIN5 are strongly associated in SMA-derived motor neurons with SMN gene mutations.
ACTA NEUROPATHOLOGICA
(2023)
Article
Geriatrics & Gerontology
Tomoki Hirunagi, Hideaki Nakatsuji, Kentaro Sahashi, Mikiyasu Yamamoto, Madoka Iida, Genki Tohnai, Naohide Kondo, Shinichiro Yamada, Ayuka Murakami, Seiya Noda, Hiroaki Adachi, Gen Sobue, Masahisa Katsuno
Summary: This study found that exercise has therapeutic potential in a mouse model of SBMA, improving motor function and survival and ameliorating neuronal and muscular histopathology. Exercise exerts its effect by activating the AMPK signaling pathway and suppressing the accumulation of polyQ-expanded AR protein in skeletal muscles and motor neurons.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
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
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
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
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
Naemeh Pourshafie, Ester Masati, Amber Lopez, Eric Bunker, Allison Snyder, Nancy A. Edwards, Audrey M. Winkelsas, Kenneth H. Fischbeck, Christopher Grunseich
Summary: This study found that SYNJ2BP is increased in diseased motor neurons and under stress in iPSC-derived motor neurons. Proteomic analysis showed that elevated SYNJ2BP alters the distribution of mitochondria and increases mitochondrial-ER membrane contact sites. Additionally, decreasing SYNJ2BP levels improves mitochondrial oxidative function in diseased motor neurons.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biology
Gavin McCluskey, Karen E. Morrison, Colette Donaghy, John McConville, Mark O. McCarron, Ferghal McVerry, William Duddy, Stephanie Duguez
Summary: This study evaluates the concentrations of serum neurofilament light (NFL) and neurofilament heavy (NFH) chain in various neurological diseases and finds that NFL can be used to differentiate these conditions and predict the progression of ALS.
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
Neurosciences
Agnes L. Nishimura, Natalia Arias
Summary: Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease caused by motor neuron degeneration. Loss of C9orf72 function and toxic effects of repeat expansions may contribute to the pathogenesis of ALS, leading to neurotransmission deficiencies.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Rocio Tejero, Mohammad Alsakkal, Luisa Hennlein, Ana M. Lopez-Cabello, Sibylle Jablonka, Lucia Tabares
Summary: In spinal muscular atrophy (SMA), mutations in the SMN1 gene reduce full-length SMN protein which causes motor neuron degeneration. Nifedipine was found to improve the function of spinal cord motor neurons and motor nerve terminals in cultured cells of SMA mice. It increased neurotransmission and prevented developmental defects in SMA neurons, indicating its potential therapeutic effects for SMA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)