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
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
Biochemistry & Molecular Biology
Laura Bianchi, Maria Sframeli, Lorenza Vantaggiato, Gian Luca Vita, Annamaria Ciranni, Francesca Polito, Rosaria Oteri, Eloisa Gitto, Fabrizio Di Giuseppe, Stefania Angelucci, Antonio Versaci, Sonia Messina, Giuseppe Vita, Luca Bini, M'hammed Aguennouz
Summary: Treatment with nusinersen in SMA type 1 patients led to a reversal trend of CSF protein profiles towards those of control donors, with significant up-regulation of apolipoprotein A1 and apolipoprotein E, as well as consistent changes in transthyretin proteoforms. These proteins play crucial roles in molecular processes aberrant in SMA, suggesting that they could serve as valuable biomarkers for assessing patient responsiveness and disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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)
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)
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
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)
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
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
Neurosciences
Rodrigo de Holanda Mendonca, Hermann Dos Santos Fernandes, Rafael Barbero Schimmelpfeng Pinto, Ciro Matsui Junior, Graziela Jorge Polido, Andre Macedo Serafim da Silva, Luis Fernando Grossklauss, Umbertina Conti Reed, Edmar Zanoteli
Summary: In SMA patients with previous spinal surgery, imaging-guided intervention is necessary for administering intrathecal nusinersen. The transforaminal technique is indicated when the interlaminar space is not available, and injections should always be guided by either CT or fluoroscopy to prevent complications.
ARQUIVOS DE NEURO-PSIQUIATRIA
(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
Rotem Orbach, Liora Sagi, Efraim Sadot, Itay Tokatly Latzer, Anna Shtamler, Tehila Zisberg, Aviva Fattal-Valevski
Summary: Longitudinal changes in CSF profiles were examined in SMA patients treated with intrathecal nusinersen. The protein concentration in CSF increased significantly during treatment, particularly in type 2 and 3 patients.
Article
Medicine, General & Internal
Andrej Belancic, Tea Strbad, Marta Kucan Stiglic, Dinko Vitezic
Summary: This study retrospectively collected clinical data of spinal muscular atrophy (SMA) patients in Croatia who received nusinersen treatment. The results showed significant improvement in pediatric patients but not in adult patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
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
Clinical Neurology
Antoon Meylemans, Pieter Depuydt, Elfride De Baere, Katrien Hertegonne, Eric Derom, Bart Dermaut, Dimitri Hemelsoet
Summary: Central hypoventilation in adult patients is a rare and life-threatening condition that can be caused by brainstem lesions or primary diseases. CCHS is a rare genetic cause of central hypoventilation and requires genetic analysis for confirmation.
ACTA NEUROLOGICA BELGICA
(2021)