Review
Clinical Neurology
Katarzyna Kotulska, Aviva Fattal-Valevski, Jana Haberlova
Summary: Spinal muscular atrophy is a neuromuscular disease caused by mutation of the SMN1 gene, but disease modifying therapies have shown effectiveness in improving motor functions of patients with SMA.
FRONTIERS IN NEUROLOGY
(2021)
Article
Medicine, Research & Experimental
John W. Day, Richard S. Finkel, Eugenio Mercuri, Kathryn J. Swoboda, Melissa Menier, Rudolf van Olden, Sitra Tauscher-Wisniewski, Jerry R. Mendell
Summary: This study examined anti-adeno-associated virus serotype 9 antibody titers in patients with spinal muscular atrophy undergoing gene therapy with Onasemnogene abeparvovec. The results suggest that most patients are eligible for treatment, but some individuals may have antibody titers that could affect therapeutic outcomes.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Economics
Rimma Velikanova, Simon van der Schans, Matthias Bischof, Rudolf Walther van Olden, Maarten Postma, Cornelis Boersma
Summary: In this study conducted in the Netherlands, including spinal muscular atrophy (SMA) in the newborn screening program was found to improve health outcomes, reduce healthcare costs, and maximize survival through early detection and treatment.
Review
Genetics & Heredity
Georgia Stimpson, Mary Chesshyre, Giovanni Baranello, Francesco Muntoni
Summary: This review discusses key features that must be considered during trial design for neuromuscular diseases, offering guidance to maximize the likelihood of trial success. These features include well-defined inclusion criteria, matching criteria, alternatives to placebo-controlled trials, and the selection of trial endpoints. These features will be particularly important in future research.
FRONTIERS IN GENETICS
(2021)
Article
Orthopedics
Kristin J. Krosschell, Sally Dunaway Young, Ilse Peterson, Mary Curry, Allison Mazzella, Jill Jarecki, Rosangel Cruz
Summary: Physical therapists play critical roles in the rehabilitation of SMA patients, and the SMA Clinical Trial Readiness Program aims to bridge the knowledge gap through education and resource provision for clinicians. This program facilitates understanding and dissemination of best practices in physical therapy for SMA patients.
Article
Clinical Neurology
Tobias Kessler, Georges Sam, Wolfgang Wick, Markus Weiler
Summary: This study assessed the changes in compound muscle action potential (CMAP) amplitudes before and during risdiplam treatment in adult patients with 5q-linked spinal muscular atrophy (SMA). The results showed that the increase in CMAP amplitudes in the median nerve was associated with clinical improvement, suggesting that it could be used as an easy-to-use electrophysiological marker to monitor treatment response.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Eduardo F. Tizzano, Vanessa Christie-Brown, Giovanni Baranello, Olga Germanenko, Allyson Gray, Marija Krstic, Charlotte Lilien, Hinal Patel, Laurent Servais, Mariacristina Scoto
Summary: Several successful clinical trials have been conducted in spinal muscular atrophy (SMA) field, leading to the approval of splicing modifiers and gene transfer therapies. In order to improve worldwide clinical trial readiness in SMA, SMA Europe initiated a clinical trial readiness project which included a face-to-face educational training for clinical specialists and physiotherapists. The training was considered successful and met the objective from participants, patients, and industry perspective.
JOURNAL OF NEUROMUSCULAR DISEASES
(2022)
Article
Economics
Thomas F. Broekhoff, Carly C. G. Sweegers, Eline M. Krijkamp, Aukje K. Mantel-Teeuwisse, Hubert G. M. Leufkens, Wim G. Goettsch, Rick A. Vreman
Summary: This study indicates that treatment with AVXS-101 may not be cost-effective under Dutch willingness-to-pay reference values. The uncertainty regarding the long-term curative properties of AVXS-101 can significantly impact the ICER, especially if relapses occur within a certain timeframe post-treatment. Decision-makers are advised to carefully consider these uncertainties when determining the price they are willing to pay.
Article
Clinical Neurology
Jeremy Slayter, Victoria Hodgkinson, Josh Lounsberry, Bernard Brais, Kristine Chapman, Angela Genge, Aaron Izenberg, Wendy Johnston, Hanns Lochmuller, Erin O'Ferrall, Gerald Pfeffer, Stephanie Plamondon, Xavier Rodrigue, Kerri Schellenberg, Christen Shoesmith, Christine Stables, Monique Taillon, Jodi Warman-Chardon, Lawrence Korngut, Colleen O'Connell
Summary: Expert panel developed a consensus-derived toolkit of OM for assessment of adults with SMA, improving monitoring and assessment of patients and enriching the quality of real-world evidence. Regular updates to the toolkit must be considered as new evidence becomes available.
JOURNAL OF NEUROMUSCULAR DISEASES
(2021)
Article
Clinical Neurology
Karlijn Bouman, Jan T. Groothuis, Jonne Doorduin, Nens van Alfen, Floris E. A. Udink ten Cate, Frederik M. A. van den Heuvel, Robin Nijveldt, Willem C. M. van Tilburg, Stan C. F. M. Buckens, Anne T. M. Dittrich, Jos M. T. Draaisma, Mirian C. H. Janssen, Erik-Jan Kamsteeg, Esmee S. B. van Kleef, Saskia Koene, Jan A. M. Smeitink, Benno Kusters, Florence H. J. van Tienen, Hubert J. M. Smeets, Baziel G. M. van Engelen, Corrie E. Erasmus, Nicol C. Voermans
Summary: The study aims to describe the natural history of patients with SELENON-RM and LAMA2-MD, select relevant clinical and functional outcome measures for clinical trial readiness, optimize clinical management through detailed description of clinical features, and establish a well-characterized baseline cohort for prospective follow-up.
Article
Biology
Liucheng Wu, Yi Wang, Lili Du, Guiqing Ji, Rui Zhou, Zeyi Zhao, Jun Chen, Shunxing Zhu
Summary: Spinal Muscular Atrophy (SMA) is a hereditary neuromuscular disease characterized by the failure to produce a full-length SMN gene. Using CRISPR/Case 9 to edit the intronic-splicing silencer sequence promotes inclusion of SMN2 exon 7, increasing SMN2 full-length gene expression.
Review
Clinical Neurology
Jeremy Slayter, Lauren Casey, Colleen O'Connell
Summary: This study aimed to identify and assess the reported evidence from the literature on Patient Reported Outcome Measures (PROMs) in adults with Spinal Muscular Atrophy (SMA). A network graph was used to visually represent the literature, PROMs, and supporting psychometric evidence, highlighting the various health domains of SMA. The study concluded that while PROMs have the potential benefits for monitoring and assessing adults with SMA, further validation studies are needed before their use in clinical decision-making.
JOURNAL OF NEUROMUSCULAR DISEASES
(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
Clinical Neurology
Eugenio Mercuri, Giovanni Baranello, Odile Boespflug-Tanguy, Liesbeth De Waele, Nathalie Goemans, Janbernd Kirschner, Riccardo Masson, Elena S. Mazzone, Astrid Pechmann, Maria Carmela Pera, Carole Vuillerot, Silvia Bader-Weder, Marianne Gerber, Ksenija Gorni, Janine Hoffart, Heidemarie Kletzl, Carmen Martin, Tammy McIver, Renata S. Scalco, Wai Yin Yeung, Laurent Servais
Summary: The study demonstrated a twofold increase in SMN protein after treatment with risdiplam, suggesting its potential effectiveness in treating spinal muscular atrophy. Additionally, the safety profile of risdiplam supported the continuation of the pivotal Part 2 study.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Astrid Pechmann, Max Behrens, Katharina Doernbrack, Adrian Tassoni, Franziska Wenzel, Sabine Stein, Sibylle Vogt, Daniela Zoeller, Gunther Bernert, Tim Hagenacker, Ulrike Schara-Schmidt, Maggie C. Walter, Meike Steinbach, Astrid Blaschek, Matthias Baumann, Manuela Baumgartner, Benedikt Becker, Marina Flotats-Bastardas, Johannes Friese, Rene Guenther, Andreas Hahn, Hanna Kuepper, Jessika Johannsen, Christoph Kamm, Jan Christoph Koch, Cornelia Koehler, Heike Koelbel, Kirsten Kolzter, Arpad von Moers, Steffen Naegel, Christoph Neuwirth, Susanne Petri, Annekathrin Roediger, Mareike Schimmel, Bertold Schrank, Gudrun Schreiber, Martin Smitka, Christian Stadler, Elisabeth Steiner, Eva Stogmann, Regina Trollmann, Matthias Tuerk, Markus Weiler, Corinna Stoltenburg, Ekkehard Willichowsky, Daniel Zeller, Andreas Ziegler, Hanns Lochmueller, Janbernd Kirschner
Summary: This study reported data from the SMArtCARE registry of ambulant patients with spinal muscular atrophy (SMA) treated with nusinersen. The results showed a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. Not only did they observe stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Review
Genetics & Heredity
Louis P. P. Garrison Jr, Andrew W. W. Lo, Richard S. S. Finkel, Patricia A. A. Deverka
Summary: The National Center for Advancing Translational Sciences held a virtual conference on gene-targeted therapies (GTTs) in 2021 to facilitate discussions on various GTT topics. The conference included social scientists, clinical scientists, and presentations on economic issues related to GTTs. The key findings include the unique challenges posed by GTTs, the need for adaptation of existing regulatory and financing systems, and the potential to accelerate progress in this field.
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2023)
Article
Medicine, General & Internal
Georgia Stimpson, Danielle Ramsey, Amy Wolfe, Anna Mayhew, Mariacristina Scoto, Giovanni Baranello, Robert Muni Lofra, Marion Main, Evelin Milev, Giorgia Coratti, Marika Pane, Valeria Sansone, Adele D'Amico, Enrico Bertini, Sonia Messina, Claudio Bruno, Emilio Albamonte, Elena Stacy Mazzone, Jacqueline Montes, Allan M. Glanzman, Zarazuela Zolkipli-Cunningham, Amy Pasternak, Tina Duong, Sally Dunaway Young, Matthew Civitello, Chiara Marini-Bettolo, John W. Day, Basil T. Darras, Darryl C. De Vivo, Richard S. Finkel, Eugenio Mercuri, Francesco Muntoni
Summary: The study investigates the motor function of participants with Spinal Muscular Atrophy (SMA) using the Revised Hammersmith Scale (RHS), and contextualizes the findings with the Hammersmith Functional Motor Scale-Expanded (HFMSE). The transitional group, including crawlers, standers, and walkers-with-assistance, shows the most significant decline in the RHS score over a year. The study highlights the importance of considering SMA type, motor function, and baseline RHS score in interpreting the change scores.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pediatrics
Claudia Brogna, Marika Pane, Giorgia Coratti, Adele D'Amico, Elena Pegoraro, Luca Bello, Valeria Ada Maria Sansone, Emilio Albamonte, Sonia Messina, Antonella Pini, Maria Grazia D'Angelo, Claudio Bruno, Tiziana Mongini, Federica Silvia Ricci, Angela Berardinelli, Roberta Battini, Riccardo Masson, Enrico Silvio Bertini, Luisa Politano, Eugenio Mercuri
Summary: This study evaluated the impact of exon skipping mutations in DMD patients, finding that PUL 2.0 can detect changes in upper limb function. Patients amenable to skipping exon 44 had smaller changes, while those amenable to skipping exon 53 had larger changes. These findings are helpful in designing clinical trials and interpreting real-world data in non-ambulant patients.
Article
Clinical Neurology
Claudia A. A. Chiriboga, Claudio Bruno, Tina Duong, Dirk Fischer, Eugenio Mercuri, Janbernd Kirschner, Anna Kostera-Pruszczyk, Birgit Jaber, Ksenija Gorni, Heidemarie Kletzl, Imogen Carruthers, Carmen Martin, Francis Warren, Renata S. S. Scalco, Kathryn R. R. Wagner, Francesco Muntoni
Summary: This study investigated the safety and pharmacodynamics of risdiplam in patients with spinal muscular atrophy (SMA) who had been previously treated. The results showed that the safety and pharmacokinetics of risdiplam in previously treated patients were consistent with treatment-naive patients.
NEUROLOGY AND THERAPY
(2023)
Article
Clinical Neurology
Thomas J. Crawford, Kathryn C. Swoboda, Darryl De Vivo, Enrico Bertini, Wuh-Liang S. Hwu, Richard Finkel, Janbernd L. Kirschner, Nancy Kuntz, Aledie Navas A. Nazario, Julie Parsons, Astrid M. Pechmann, M. Monique M. J. Ryan, Russell Butterfield, Haluk Topaloglu, Tawfeg A. Ben-Omran, Valeria Sansone, Yuh-Jyh Jong, Francy Shu, Cong Zhu, Stephanie R. Raynaud, Tiffany D. Lago, Angela Paradis, Richard Foster, Russell Chin, Zdenek Berger, NURTURE Study Grp
Summary: The NURTURE study provides evidence for the effectiveness and safety of early treatment with nusinersen in children with presymptomatic spinal muscular atrophy. The results demonstrate the durability of treatment effects and the potential for improved outcomes in motor function and survival.
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
Pediatrics
Laura Antonaci, Maria Carmela Pera, Eugenio Mercuri
Summary: The natural history of spinal muscular atrophy has been significantly influenced by improved care standards and the availability of disease-modifying therapies. This paper aims to present the current therapeutic scenario and challenges associated with new phenotypes emerging years after the introduction of therapies. It also includes a review of real-world data, offering insights into the safety and effectiveness of the drugs beyond clinical trials. The paper emphasizes future perspectives, including ongoing clinical trials and advancements in the use of available drugs.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Neurosciences
David C. Schorling, Rainer Rawer, Imke Kuhlmann, Cornelia Mueller, Astrid Pechmann, Janbernd Kirschner
Summary: The study aimed to establish reference data for the 4 stair climb test (4SC), and for mechanographic analysis of ascent (4SC-Up) and descent (4SC-Dn) in healthy children and adolescents. The results showed that mechanographic analysis of the 4SC appears to be a promising tool for evaluating muscle strength and function of the lower extremities.
JOURNAL OF MUSCULOSKELETAL & NEURONAL INTERACTIONS
(2023)
Article
Neurosciences
Vito Luigi Colona, Enrico Bertini, Maria Cristina Digilio, Adele D'Amico, Antonio Novelli, Stefano Pro, Elisa Pisaneschi, Francesco Nicita
Summary: POLR3B gene encodes the RPC2 subunit of RNA polymerase III, and pathogenic variants are associated with various disorders, including hypomyelinating leukodystrophy and Charcot-Marie-Tooth syndrome type 1I. In this study, a new variant in the POLR3B gene was identified in a patient with developmental delay, epilepsy, and polyneuropathy.
Article
Genetics & Heredity
Aurelien Perrin, Corinne Metay, Marco Savarese, Rabah Ben Yaou, German Demidov, Isabelle Nelson, Guilhem Sole, Yann Pereon, Enrico Silvio Bertini, Fabiana Fattori, Adele D'Amico, Federica Ricci, Mira Ginsberg, Andreea Seferian, Odile Boespflug-Tanguy, Laurent Servais, Francoise Chapon, Emmeline Lagrange, Karen Gaudon, Adrien Bloch, Robin Ghanem, Lucie Guyant-Marechal, Mridul Johari, Charles Van Goethem, Michel Fardeau, Raul Juntas Morales, Casie A. Genetti, Minttu Marttila, Michel Koenig, Alan Beggs, Bjarne Udd, Gisele Bonne, Mireille Cossee
Summary: Titinopathies are complex neuromuscular pathologies caused by mutations in the titin gene (TTN). A study identified multiple deletion-type CNVs in the TTN gene in several families, revealing new genotype-phenotype associations, mainly distal myopathy.
JOURNAL OF MEDICAL GENETICS
(2023)
