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1,226 results on '"Day, John W."'

1. Cardiac and pulmonary findings in dysferlinopathy: A 3‐year, longitudinal study

Author

Moore, Ursula, Fernandez‐Torron, Roberto, Jacobs, Marni, Gordish‐Dressman, Heather, Diaz‐Manera, Jordi, James, Meredith K, Mayhew, Anna G, Harris, Elizabeth, Guglieri, Michela, Rufibach, Laura E, Feng, Jia, Blamire, Andrew M, Carlier, Pierre G, Spuler, Simone, Day, John W, Jones, Kristi J, Bharucha‐Goebel, Diana X, Salort‐Campana, Emmanuelle, Pestronk, Alan, Walter, Maggie C, Paradas, Carmen, Stojkovic, Tanya, Mori‐Yoshimura, Madoka, Bravver, Elena, Pegoraro, Elena, Lowes, Linda Pax, Mendell, Jerry R, Bushby, Kate, Consortium, The Jain COS, Bourke, John, and Straub, Volker

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Cardiovascular, Heart Disease, Lung, Clinical Research, Electrocardiography, Female, Humans, Longitudinal Studies, Male, Muscular Dystrophies, Limb-Girdle, Phenotype, Jain COS Consortium, Miyoshi myopathy, cardiac, dysferlin, limb girdle muscular dystrophy R2, respiratory, Medical and Health Sciences, Neurology & Neurosurgery, Biological sciences, Biomedical and clinical sciences
Abstract

Introduction/aimsThere is debate about whether and to what extent either respiratory or cardiac dysfunction occurs in patients with dysferlinopathy. This study aimed to establish definitively whether dysfunction in either system is part of the dysferlinopathy phenotype.MethodsAs part of the Jain Foundation's International Clinical Outcome Study (COS) for dysferlinopathy, objective measures of respiratory and cardiac function were collected twice, with a 3-y interval between tests, in 188 genetically confirmed patients aged 11-86 y (53% female). Measures included forced vital capacity (FVC), electrocardiogram (ECG), and echocardiogram (echo).ResultsMean FVC was 90% predicted at baseline, decreasing to 88% at year 3. FVC was less than 80% predicted in 44 patients (24%) at baseline and 48 patients (30%) by year 3, including ambulant participants. ECGs showed P-wave abnormalities indicative of delayed trans-atrial conduction in 58% of patients at baseline, representing a risk for developing atrial flutter or fibrillation. The prevalence of impaired left ventricular function or hypertrophy was comparable to that in the general population.DiscussionThese results demonstrate clinically significant respiratory impairment and abnormal atrial conduction in some patients with dysferlinopathy. Therefore, we recommend that annual or biannual follow-up should include FVC measurement, enquiry about arrhythmia symptoms and peripheral pulse palpation to assess cardiac rhythm. However, periodic specialist cardiac review is probably not warranted unless prompted by symptoms or abnormal pulse findings.

Published
2022

2. Intron mutations and early transcription termination in Duchenne and Becker muscular dystrophy.

Author

Waldrop, Megan A, Moore, Steven A, Mathews, Katherine D, Darbro, Benjamin W, Medne, Livja, Finkel, Richard, Connolly, Anne M, Crawford, Thomas O, Drachman, Daniel, Wein, Nicolas, Habib, Ali A, Krzesniak-Swinarska, Monika A, Zaidman, Craig M, Collins, James J, Jokela, Manu, Udd, Bjarne, Day, John W, Ortiz-Guerrero, Gloria, Statland, Jeff, Butterfield, Russell J, Dunn, Diane M, Weiss, Robert B, and Flanigan, Kevin M

Subjects
Humans, Muscular Dystrophy, Duchenne, Dystrophin, RNA Splice Sites, Mutation, Introns, Becker muscular dystrophy, Duchenne muscular dystrophy, deep intronic, pseudoexon, telescripting, transcription termination, Muscular Dystrophy, Biotechnology, Human Genome, Genetics, Intellectual and Developmental Disabilities (IDD), Duchenne/ Becker Muscular Dystrophy, Brain Disorders, Rare Diseases, Pediatric, Musculoskeletal, Clinical Sciences, Genetics & Heredity
Abstract

DMD pathogenic variants for Duchenne and Becker muscular dystrophy are detectable with high sensitivity by standard clinical exome analyses of genomic DNA. However, up to 7% of DMD mutations are deep intronic and analysis of muscle-derived RNA is an important diagnostic step for patients who have negative genomic testing but abnormal dystrophin expression in muscle. In this study, muscle biopsies were evaluated from 19 patients with clinical features of a dystrophinopathy, but negative clinical DMD mutation analysis. Reverse transcription-polymerase chain reaction or high-throughput RNA sequencing methods identified 19 mutations with one of three pathogenic pseudoexon types: deep intronic point mutations, deletions or insertions, and translocations. In association with point mutations creating intronic splice acceptor sites, we observed the first examples of DMD pseudo 3'-terminal exon mutations causing high efficiency transcription termination within introns. This connection between splicing and premature transcription termination is reminiscent of U1 snRNP-mediating telescripting in sustaining RNA polymerase II elongation across large genes, such as DMD. We propose a novel classification of three distinct types of mutations identifiable by muscle RNA analysis, each of which differ in potential treatment approaches. Recognition and appropriate characterization may lead to therapies directed toward full-length dystrophin expression for some patients.

Published
2022

4. Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)

Author

Oskoui, Maryam, Day, John W., Deconinck, Nicolas, Mazzone, Elena S., Nascimento, Andres, Saito, Kayoko, Vuillerot, Carole, Baranello, Giovanni, Goemans, Nathalie, Kirschner, Janbernd, Kostera-Pruszczyk, Anna, Servais, Laurent, Papp, Gergely, Gorni, Ksenija, Kletzl, Heidemarie, Martin, Carmen, McIver, Tammy, Scalco, Renata S., Staunton, Hannah, Yeung, Wai Yin, Fontoura, Paulo, and Mercuri, Eugenio

Published
2023
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5. Increased tissue stiffness triggers contractile dysfunction and telomere shortening in dystrophic cardiomyocytes

Author

Chang, Alex CY, Pardon, Gaspard, Chang, Andrew CH, Wu, Haodi, Ong, Sang-Ging, Eguchi, Asuka, Ancel, Sara, Holbrook, Colin, Ramunas, John, Ribeiro, Alexandre JS, LaGory, Edward L, Wang, Honghui, Koleckar, Kassie, Giaccia, Amato, Mack, David L, Childers, Martin K, Denning, Chris, Day, John W, Wu, Joseph C, Pruitt, Beth L, and Blau, Helen M

Subjects
Biochemistry and Cell Biology, Biological Sciences, Orphan Drug, Pediatric, Muscular Dystrophy, Brain Disorders, Rare Diseases, Duchenne/ Becker Muscular Dystrophy, Cardiovascular, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell, Bioengineering, Intellectual and Developmental Disabilities (IDD), Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Biomarkers, Cardiomyopathies, Cell Differentiation, Cells, Cultured, Cellular Microenvironment, Culture Media, Conditioned, Fibrosis, Fluorescent Antibody Technique, Gene Expression, Humans, Immunophenotyping, Induced Pluripotent Stem Cells, Mechanical Phenomena, Muscular Dystrophies, Muscular Dystrophy, Duchenne, Myocardial Contraction, Myocytes, Cardiac, Telomere Shortening, DMD, dilated cardiomyopathy, fibrosis, hiPSC-CM, telomere, Clinical Sciences, Biochemistry and cell biology
Abstract

Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disease that is associated with severe progressive muscle degeneration culminating in death due to cardiorespiratory failure. We previously observed an unexpected proliferation-independent telomere shortening in cardiomyocytes of a DMD mouse model. Here, we provide mechanistic insights using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using traction force microscopy, we show that DMD hiPSC-CMs exhibit deficits in force generation on fibrotic-like bioengineered hydrogels, aberrant calcium handling, and increased reactive oxygen species levels. Furthermore, we observed a progressive post-mitotic telomere shortening in DMD hiPSC-CMs coincident with downregulation of shelterin complex, telomere capping proteins, and activation of the p53 DNA damage response. This telomere shortening is blocked by blebbistatin, which inhibits contraction in DMD cardiomyocytes. Our studies underscore the role of fibrotic stiffening in the etiology of DMD cardiomyopathy. In addition, our data indicate that telomere shortening is progressive, contraction dependent, and mechanosensitive, and suggest points of therapeutic intervention.

Published
2021

6. Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study.

Author

Rudnicki, Stacy A, Andrews, Jinsy A, Duong, Tina, Cockroft, Bettina M, Malik, Fady I, Meng, Lisa, Wei, Jenny, Wolff, Andrew A, Genge, Angela, Johnson, Nicholas E, Tesi-Rocha, Carolina, Connolly, Anne M, Darras, Basil T, Felice, Kevin, Finkel, Richard S, Shieh, Perry B, Mah, Jean K, Statland, Jeffrey, Campbell, Craig, Habib, Ali A, Kuntz, Nancy L, Oskoui, Maryam, and Day, John W

Subjects
Muscle, Skeletal, Humans, Muscular Atrophy, Spinal, Troponin I, Drugs, Investigational, Cohort Studies, Double-Blind Method, Adolescent, Adult, Aged, Middle Aged, Child, Female, Male, Young Adult, Walk Test, Reldesemtiv, pharmacodynamics, pharmacokinetics, six-minute walk test, spinal muscular atrophy clinical trial, Clinical Research, Clinical Trials and Supportive Activities, Rare Diseases, 6.1 Pharmaceuticals, Neurosciences, Pharmacology and Pharmaceutical Sciences, Public Health and Health Services, Neurology & Neurosurgery
Abstract

This phase 2, double-blind, placebo-controlled, hypothesis-generating study evaluated the effects of oral reldesemtiv, a fast skeletal muscle troponin activator, in patients with spinal muscular atrophy (SMA). Patients ≥ 12 years of age with type II, III, or IV SMA were randomized into 2 sequential, ascending reldesemtiv dosing cohorts (cohort 1: 150 mg bid or placebo [2:1]; cohort 2: 450 mg bid or placebo [2:1]). The primary objective was to determine potential pharmacodynamic effects of reldesemtiv on 8 outcome measures in SMA, including 6-minute walk distance (6MWD) and maximum expiratory pressure (MEP). Changes from baseline to weeks 4 and 8 were determined. Pharmacokinetics and safety were also evaluated. Patients were randomized to reldesemtiv 150 mg, 450 mg, or placebo (24, 20, and 26, respectively). The change from baseline in 6MWD was greater for reldesemtiv 450 mg than for placebo at weeks 4 and 8 (least squares [LS] mean difference, 35.6 m [p = 0.0037] and 24.9 m [p = 0.058], respectively). Changes from baseline in MEP at week 8 on reldesemtiv 150 and 450 mg were significantly greater than those on placebo (LS mean differences, 11.7 [p = 0.038] and 13.2 cm H2O [p = 0.03], respectively). For 6MWD and MEP, significant changes from placebo were seen in the highest reldesemtiv peak plasma concentration quartile (Cmax > 3.29 μg/mL; LS mean differences, 43.3 m [p = 0.010] and 28.8 cm H2O [p = 0.0002], respectively). Both dose levels of reldesemtiv were well tolerated. Results suggest reldesemtiv may offer clinical benefit and support evaluation in larger SMA patient populations.

Published
2021

9. Correction to: Two‑year efficacy and safety of risdiplam in patients with type 2 or non‑ambulant type 3 spinal muscular atrophy (SMA)

Author

Oskoui, Maryam, Day, John W., Deconinck, Nicolas, Mazzone, Elena S., Nascimento, Andres, Saito, Kayoko, Vuillerot, Carole, Baranello, Giovanni, Goemans, Nathalie, Kirschner, Janbernd, Kostera-Pruszczyk, Anna, Servais, Laurent, Papp, Gergely, Gorni, Ksenija, Kletzl, Heidemarie, Martin, Carmen, McIver, Tammy, Scalco, Renata S., Staunton, Hannah, Yeung, Wai Yin, Fontoura, Paulo, and Mercuri, Eugenio

Published
2023
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10. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial

Author

Volpe, Joseph J., Posner, John, Kellner, Ulrich, Quinlivan, Rosaline, Daron, Aurore, Delstanche, Stéphanie, Bruninx, Romain, Dal Farra, Fabian, Schneider, Olivier, Deconinck, Nicolas, Balikova, Irina, Delbeke, Patricia, Joniau, Inge, Tahon, Valentine, Wittevrongel, Sylvia, De Vos, Elke, Goemans, Nathalie, Casteels, Ingele, De Waele, Liesbeth, Cassiman, Catherine, Prové, Lies, Kinoo, David, Vancampenhout, Lisa, Van Den Hauwe, Marleen, Van Impe, Annelies, Prufer de Queiroz Campos Araujo, Alexandra, Chacon Pereira, Aline, Nardes, Flávia, Haefeli, Lorena, Rossetto, Julia, Ferreira Rebel, Marcos, Almeida Pereira, Jaqueline, Campbell, Craig, Sharan, Sapna, McDonald, Wendy, Scholtes, Cheryl, Mah, Jean, Sframeli, Maria, Chiu, Angela, Hagel, Jane, Oskoui, Maryam, Beneish, Raquel, Cariou-Palmer, Gaela, Pham, Connie, Toffoli, Daniela, Arpin, Stephanie, Turgeon Desilets, Sarah, Wang, Yi, Hu, Chaoping, Huan, Jianfeng, Qian, Chen, Shen, Li, Xiao, Ying, Zhou, Zhenxuan, Li, Hui, Wang, Sujuan, Xiong, Hui, Chang, Xingzhi, Dong, Hui, Liu, Ying, Sang, Tian, Wei, Cuijie, Wen, Jing, Cao, Yiwen, Ly, Xingyao, Zhao, Jingjing, Li, Wenzhu, Qin, Lun, Barisic, Nina, Galiot Delic, Martina, Ivkic, Petra Kristina, Vukojevic, Nenad, Kern, Ivana, Najdanovic, Boris, Skugor, Marin, Servais, Laurent, Boespflug-Tanguy, Odile, Gidaro, Teresa, Seferian, Andreea, De Lucia, Silvana, Barreau, Emmanuel, Mnafek, Nabila, Momtchilova, Marta Milkova, Peche, Helene, Valherie, Carole, Grange, Allison, Lilien, Charlotte, Milascevic, Darko, Tachibana, Shotaro, Ravelli, Claudia, Cardas, Ruxandra, Taytard, Jessica, Aubertin, Guillaume, Vanden Brande, Laure, Davion, Jean-Baptiste, Coopman, Stephanie, Bouacha, Ikram, Debruyne, Philippe, Defoort, Sabine, Derlyn, Gilles, Leroy, Florian, Danjoux, Loïc, Guilbaud, Julie, Desguerre, Isabelle, Barnérias, Christine, Semeraro, Michaela, Bremond-Gignac, Dominique, Bruere, Lenaic, Rateaux, Maxence, Deladrière, Élodie, Germa, Virginie, Pereon, Yann, Mercie, Sandra, Billaud, Fanny, Le Goff, Lucie, Letellier, Guy, Vuillerot, Carole, Portefaix, Aurélie, De-Montferrand, Camille, Le-Goff, Laure, Fontaine, Stephanie, Saidi, Manel, Bouzid, Nabil, Barriere, Aurélie, Tinat, Marie, Kirschner, Janbernd, Dreesbach, Michelle, Lagréze, Wolf, Michaelis, Bettina, Molnar, Fanni, Seger, Dorina, Vogt, Sibylle, Bertini, Enrico, D'Amico, Adele, Petroni, Sergio, Bonetti, Anna Maria, Carlesi, Adelina, Mizzoni, Irene, Bruno, Claudio, Priolo, Enrico, Rao, Giuseppe, Morando, Simone, Tacchetti, Paola, Zuffi, Ambra, Comi, Giacomo Pietro, Brusa, Roberta, Corti, Stefania, Daniele, Velardo, Govoni, Alessandra, Magri, Francesca, Minorini, Valeria, Osnaghi, Silvia Gabriella, Abbati, Francesca, Fassini, Federica, Foa, Michaela, Lopopolo, Amaqlia, Meneri, Megi, Zoppas, Francesca, Parente, Valeria, Baranello, Giovanni, Masson, Riccardo, Bianchi Marzoli, Stefania, Santarsiero, Diletta, Garcia Sierra, Myriam, Tremolada, Gemma, Arnoldi, Maria Teresa, Vigano, Marta, Zanin, Riccardo, Mercuri, Eugenio, Antonaci, Laura, de Sanctis, Roberto, Pane, Marika, Pera, Maria Carmela, Amorelli, Giulia Maria, Barresi, Costanza, D'Amico, Gugliemo, Orazi, Lorenzo, Coratti, Giorgia, Haginoya, Kazuhiro, Kato, Atsuko, Morishita, Yuko, Kira, Ryutaro, Akiyama, Kiyomu, Goto, Miwako, Mori, Yujiro, Okamoto, Misato, Tsutsui, Saki, Takatsuji, Yuta, Tanaka, Aya, Komaki, Hirofumi, Omori, Miina, Suzuki, Ippei, Takeuchi, Mizuki, Todoroki, Daisuke, Watanabe, Seji, Matsubayashi, Tomoko, Inakazu, Emi, Nagura, Hiroe, Suzuki, Akira, Usui, Manami, Ishikawa, Nobutsune, Harada, Yousuke, Fudeyasu, Kenishi, Hirata, Kazuhiko, Michiue, Kana, Ueda, Kazuyuki, Saito, Kayoko, Fujitani, Junko, Arakawa, Reiko, Takano, Kozue, Yashiro, Shigeko, Seki, Maiko, Sano, Nozomi, Fukuyama, Koji, Matsumoto, Yuki, Miyazaki, Hirofumi, Shibata, Minoru, Kobayashi, Kyoko, Nakamura, Yukie, Takeshima, Yasuhiro, Kuma, Moe, Kostera-Pruszczyk, Anna, Fraczek, Anna, Jedrzejowska, Maria, Lusakowska, Anna, Czeszyk-Piotrowicz, Agnieszka, Hautz, Wojciech, Rakusiewicz, Klaudia, Burlewicz, Malgorzata, Gierlak-Wojcicka, Zuzanna, Kepa, Malwina, Sikorski, Adam, Sobieraj, Marcin, Mazurkiewicz-Beldzinska, Maria, Lemska, Anna, Modrzejewska, Sandra, Koberda, Mateusz, Stodolska-Koberda, Urszula, Waskowska, Agnieszka, Kolendo, Jagoda, Sobierajska-Rek, Agnieszka, Steinborn, Barbara, Dalz, Magdalena, Grabowska, Julia, Hajduk, Wojciech, Janasiewicz-Karachitos, Justyna, Klimas, Monika, Stopa, Marcin, Gajewska, Ewa, Pusz, Beata, Vlodavets, Dmitry, Melnik, Evgenia, Leppenen, Natalya, Yupatova, Nataliya, Monakhova, Anastasya, Papina, Yulia, Shidlovsckaia, Olga, Milic Rasic, Vedrana, Brankovic, Vesna, Kosac, Ana, Djokic, Olivera, Jakšic, Vesna, Pepic, Ana, Martinovic, Jelena, Munell Casadesus, Francina, Tizzano, Eduardo, Martín Begué, Nieves, Wolley Dod, Charlotte, Subira, Olaia, Planas Pascual, Bernat, Toro Tamargo, Esther, Madruga Garrido, Marcos, Medina Romero, José David, Salinas, Marta Peña, Nascimento Osorio, Andrés, Díaz Cortés, Ana, Jiménez Gañan, Enrique, Suh, Simone Dowon, Medina Cantillo, Julita, Moya, Obdulia, Padros, Nuria, Urraca, Sandra Roca, Valdivia, Hugo Gonzalez, Pascual Pascual, Samuel, de Manuel, Sofía, Martin, Susana Noval, Burnham, Paul, Espinosa, Sandra, Moreno, Mercedes Martinez, Topaloglu, Haluk, Oncel, Ibrahim, Eroglu Ertugru, Nesibe, Konuskan, Bahadir, Eldem, Bora, Kadayifçilar, Sibel, Alemdaroglu, Ipek, Karaduman, Aynur Ayse, Yilmaz, Oznur Tunca, Bilgin, Neslihan, Sari, Seher, Chiriboga, Claudia, Lee, John J., Rome-Martin, Donnielle, Day, John W., Beres, Shannon, Duong, Tina, Gee, Richard, Dunaway Young, Sally, Fuerst-Recktenwald, Sabine, Marquet, Anne, Muelhardt, Nicoletta, Trundell, Dylan, Mazzone, Elena S, Nascimento, Andres, Gerber, Marianne, Gorni, Ksenija, Khwaja, Omar, Kletzl, Heidemarie, Scalco, Renata S, Staunton, Hannah, Yeung, Wai Yin, Martin, Carmen, Fontoura, Paulo, and Day, John W

Published
2022
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12. Expanding the muscle imaging spectrum in dysferlinopathy: description of an outlier population from the classical MRI pattern

Author

Llansó, Laura, Moore, Ursula, Bolano-Diaz, Carla, James, Meredith, Blamire, Andrew M., Carlier, Pierre G., Rufibach, Laura, Gordish-Dressman, Heather, Boyle, Georgina, Hilsden, Heather, Day, John W., Jones, Kristi J., Bharucha-Goebel, Diana X., Salort-Campana, Emmanuelle, Pestronk, Alan, Walter, Maggie C., Paradas, Carmen, Stojkovic, Tanya, Mori-Yoshimura, Madoka, Bravver, Elena, Pegoraro, Elena, Mendell, Jerry R., Straub, Volker, and Díaz-Manera, Jordi

Published
2023
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15. Introduction

Author

Day, John W., Hunter, Rachael G., Clark, H. C., Day, J. W., editor, Hunter, R. G., editor, and Clark, H. C., editor

Published
2022
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17. Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease

Author

Kishnani, Priya S, Gibson, James B, Gambello, Michael J, Hillman, Richard, Stockton, David W, Kronn, David, Leslie, Nancy D, Pena, Loren DM, Tanpaiboon, Pranoot, Day, John W, Wang, Raymond Y, Goldstein, Jennifer L, An Haack, Kristina, Sparks, Susan E, Zhao, Yang, and Hahn, Si Houn

Subjects
Biological Sciences, Genetics, Digestive Diseases, Clinical Research, Liver Disease, Chronic Liver Disease and Cirrhosis, Pediatric, Adolescent, Child, Child, Preschool, Cohort Studies, Enzyme Replacement Therapy, Female, Genotype, Glycogen Storage Disease Type II, Humans, Infant, Male, Phenotype, Prospective Studies, United States, alpha-Glucosidases, alglucosidase alfa, glycogenosis type 2, GAA pathogenic variants, infantile-onset Pompe disease, late-onset Pompe disease, Pompe ADVANCE Study Consortium, Clinical Sciences, Genetics & Heredity
Abstract

PurposeTo characterize clinical characteristics and genotypes of patients in the ADVANCE study of 4000 L-scale alglucosidase alfa (NCT01526785), the largest prospective United States Pompe disease cohort to date.MethodsPatients aged ≥1 year with confirmed Pompe disease previously receiving 160 L alglucosidase alfa were eligible. GAA genotypes were determined before/at enrollment. Baseline assessments included histories/physical exams, Gross Motor Function Measure-88 (GMFM-88), pulmonary function tests, and cardiac assessments.ResultsOf 113 enrollees (60 male/53 female) aged 1-18 years, 87 had infantile-onset Pompe disease (IOPD) and 26 late-onset (LOPD). One hundred eight enrollees with GAA genotypes had 215 pathogenic variants (220 including combinations): 118 missense (4 combinations), 23 splice, 35 nonsense, 34 insertions/deletions, 9 duplications (1 combination), 6 other; c.2560C>T (n = 23), c.-32-13T>G (n = 13), and c.525delT (n = 12) were most common. Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material-negative. All IOPD and 6/26 LOPD patients had cardiac involvement, all without c.-32-13T>G. Thirty-two (26 IOPD, 6 LOPD) were invasively ventilated. GMFM-88 total %scores (mean ± SD, median, range): overall 46.3 ± 33.0% (47.9%, 0.0-100.0%), IOPD 41.6 ± 31.64% (38.9%, 0.0-99.7%), LOPD: 61.8 ± 33.2 (70.9%, 0.0-100.0%).ConclusionADVANCE, a uniformly assessed cohort comprising most US children and adolescents with treated Pompe disease, expands understanding of the phenotype and observed variants in the United States.

Published
2019

18. Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial

Author

Thornton, Charles A, Moxley, Richard Thomas, III, Eichinger, Katy, Heatwole, Chad, Mignon, Laurence, Arnold, W David, Ashizawa, Tetsuo, Day, John W, Dent, Gersham, Tanner, Matthew K, Duong, Tina, Greene, Ericka P, Herbelin, Laura, Johnson, Nicholas E, King, Wendy, Kissel, John T, Leung, Doris G, Lott, Donovan J, Norris, Daniel A, Pucillo, Evan M, Schell, Wendy, Statland, Jeffrey M, Stinson, Nikia, Subramony, Sub H, Xia, Shuting, Bishop, Kathie M, and Bennett, C Frank

Published
2023
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19. Myostatin and follistatin as monitoring and prognostic biomarkers in dysferlinopathy

Author

Moore, Ursula, Fernández-Simón, Esther, Schiava, Marianela, Cox, Dan, Gordish-Dressman, Heather, James, Meredith K., Mayhew, Anna, Wilson, Ian, Guglieri, Michela, Rufibach, Laura, Blamire, Andrew, Carlier, Pierre G., Mori-Yoshimura, Madoka, Day, John W., Jones, Kristi J., Bharucha-Goebel, Diana X., Salort-Campana, Emmanuelle, Pestronk, Alan, Walter, Maggie C., Paradas, Carmen, Stojkovic, Tanya, Bravver, Elena, Pegoraro, Elena, Mendell, Jerry R., Bushby, Kate, Diaz-Manera, Jordi, and Straub, Volker

Published
2023
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21. Beyond Contractures in Spinal Muscular Atrophy: Identifying Lower-Limb Joint Hypermobility

Author

Harding, Elizabeth R., primary, Kanner, Cara H., additional, Pasternak, Amy, additional, Glanzman, Allan M., additional, Dunaway Young, Sally, additional, Rao, Ashwini K., additional, McDermott, Michael P., additional, Zolkipli-Cunningham, Zarazuela, additional, Day, John W., additional, Finkel, Richard S., additional, Darras, Basil T., additional, De Vivo, Darryl C., additional, and Montes, Jacqueline, additional

Published
2024
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22. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial

Author

Volpe, Joseph J, Posner, John, Kellner, Ulrich, Quinlivan, Rosaline, Gerber, Marianne, Khwaja, Omar, Scalco, Renata S, Seabrook, Timothy, Koch, Armin, Balikova, Irina, Joniau, Inge, Accou, Geraldine, Tahon, Valentine, Wittevrongel, Sylvia, De Vos, Elke, de Holanda Mendonça, Rodrigo, Matsui Jr, Ciro, Fornazieri Darcie, Ana Letícia, Machado, Cleide, Kiyoko Oyamada, Maria, Martini, Joyce, Polido, Graziela, Rodrigues Iannicelli, Juliana, Caires de Oliveira Achili Ferreira, Juliana, Hu, Chaoping, Zhu, Xiaomei, Qian, Chen, Shen, Li, Li, Hui, Shi, Yiyun, Zhou, Shuizhen, Xiao, Ying, Zhou, Zhenxuan, Wang, Sujuan, Sang, Tian, Wei, Cuijie, Dong, Hui, Cao, Yiwen, Wen, Jing, Li, Wenzhu, Qin, Lun, Barisic, Nina, Celovec, Ivan, Galiot Delic, Martina, Ivkic, Petra Kristina, Vukojevic, Nenad, Kern, Ivana, Najdanovic, Boris, Skugor, Marin, Tomas, Josipa, Boespflug-Tanguy, Odile, De Lucia, Silvana, Seferian, Andrea, Barreau, Emmanuel, Mnafek, Nabila, Peche, Helene, Grange, Allison, Trang Nguyen, Diem, Milascevic, Darko, Tachibana, Shotaro, Pagliano, Emanuela, Bianchi Marzoli, Stefania, Santarsiero, Diletta, Garcia Sierra, Myriam, Tremolada, Gemma, Arnoldi, Maria Teresa, Vigano, Marta, Dosi, Claudia, Zanin, Riccardo, Schembri, Veronica, Brolatti, Noemi, Rao, Giuseppe, Tassara, Elisa, Morando, Simone, Tacchetti, Paola, Pedemonte, Marina, Priolo, Enrico, Sposetti, Lorenza, Comi, Giacomo Pietro, Govoni, Alessandra, Osnaghi, Silvia Gabriella, Minorini, Valeria, Abbati, Francesca, Fassini, Federica, Foa, Michaela, Lopopolo, Amalia, Pane, Marika, Palermo, Concetta, Pera, Maria Carmela, Amorelli, Giulia Maria, Barresi, Costanza, D'Amico, Guglielmo, Orazi, Lorenzo, Coratti, Giorgia, Leone, Daniela, Laura, Antonaci, De Sanctis, Roberto, Berti, Beatrice, Kimura, Naoki, Takeshima, Yasuhiro, Shimomura, Hideki, Lee, Tomoko, Gomi, Fumi, Morimatsu, Takanobu, Furukawa, Toru, Stodolska-Koberda, Urszula, Waskowska, Agnieszka, Kolendo, Jagoda, Sobierajska-Rek, Agnieszka, Modrzejewska, Sandra, Lemska, Anna, Melnik, Evgenia, Artemyeva, Svetlana, Leppenen, Natalya, Yupatova, Nataliya, Monakhova, Anastasya, Papina, Yulia, Shidlovsckaia, Olga, Litvinova, Elena, Enzmann, Cornelia, Galiart, Elea, Gugleta, Konstantin, Wondrusch Haschke, Christine, Topaloglu, Haluk, Oncel, Ibrahim, Ertugrul, Nesibe Eroglu, Konuskan, Bahadir, Eldem, Bora, Kadayifçilar, Sibel, Alemdaroglu, Ipek, Sari, Seher, Bilgin, Neslihan, Karaduman, Aynur Ayse, Sarikaya, Fatma Gokcem Yildiz, Graham, Robert J, Ghosh, Partha, Casavant, David, Levine, Alexis, Titus, Rachael, Engelbrekt, Amanda, Ambrosio, Lucia, Fulton, Anne, Baglieri, Anna Maria, Dias, Courtney, Maczek, Elizabeth, Pasternak, Amy, Beres, Shannon, Duong, Tina, Gee, Richard, Young, Sally, Masson, Riccardo, Mazurkiewicz-Bełdzińska, Maria, Rose, Kristy, Servais, Laurent, Xiong, Hui, Zanoteli, Edmar, Baranello, Giovanni, Bruno, Claudio, Day, John W, Deconinck, Nicolas, Klein, Andrea, Mercuri, Eugenio, Vlodavets, Dmitry, Wang, Yi, Dodman, Angela, El-Khairi, Muna, Gorni, Ksenija, Jaber, Birgit, Kletzl, Heidemarie, Gaki, Eleni, Fontoura, Paulo, and Darras, Basil T

Published
2022
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24. Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: results from the 36-month TOPAZ study.

Author

Crawford, Thomas O., Day, John W., De Vivo, Darryl C., Krueger, Jena M., Mercuri, Eugenio, Nascimento, Andres, Pasternak, Amy, Mazzone, Elena Stacy, Duong, Tina, Guochen Song, Marantz, Jing L., Baver, Scott, Dongzi Yu, Lan Liu, and Darras, Basil T.

Subjects
SPINAL muscular atrophy, COMPUTER adaptive testing, RESPIRATORY infections, COVID-19, FATIGUE (Physiology)
Abstract

Background and purpose: At 12 months in the phase 2 TOPAZ study, treatment with apitegromab was associated with both an improved motor function in patients with Type 2 or 3 spinal muscular atrophy (SMA) and with a favorable safety profile. This manuscript reports the extended efficacy and safety in the nonambulatory group of the TOPAZ study at 36 months. Methods: Patients who completed the primary study (NCT03921528) could enroll in an open-label extension, during which patients received apitegromab 20 mg/kg by intravenous infusion every 4 weeks. Patients were assessed periodically via the Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), World Health Organization (WHO) motor development milestones, Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) Daily Activities and Mobility domains, and Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire. Results: Of the 58 patients enrolled in TOPAZ, 35 were nonambulatory (mean age 7.3 years). The mean change at 36 months in HFMSE score from baseline was +4.0 (standard deviation [SD]: 7.54), and + 2.4 (3.24) for RULM score (excluding n = 7 after scoliosis surgery). Caregiver-reported outcomes (PEDI-CAT and PROMIS Fatigue) showed improvements from baseline over 36 months. In addition, most patients (28/32) improved or maintained WHO motor milestones achieved at baseline. The most frequently reported treatment-emergent adverse events were pyrexia (48.6%), nasopharyngitis (45.7%), COVID-19 infection (40.0%), vomiting (40.0%), and upper respiratory tract infection (31.4%). Conclusion: The benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Telomere shortening is a hallmark of genetic cardiomyopathies

Author

Chang, Alex CY, Chang, Andrew CH, Kirillova, Anna, Sasagawa, Koki, Su, Willis, Weber, Gerhard, Lin, Jue, Termglinchan, Vittavat, Karakikes, Ioannis, Seeger, Timon, Dainis, Alexandra M, Hinson, John T, Seidman, Jonathan, Seidman, Christine E, Day, John W, Ashley, Euan, Wu, Joseph C, and Blau, Helen M

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Clinical Research, Orphan Drug, Cardiovascular, Heart Disease, Genetics, Stem Cell Research, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic, Familial, Cell Division, Female, Humans, Induced Pluripotent Stem Cells, Male, Muscle Proteins, Mutation, Telomere Shortening, telomere, dilated cardiomyopathy, hypertrophy cardiomyopathy, hiPSC-CM
Abstract

This study demonstrates that significantly shortened telomeres are a hallmark of cardiomyocytes (CMs) from individuals with end-stage hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) as a result of heritable defects in cardiac proteins critical to contractile function. Positioned at the ends of chromosomes, telomeres are DNA repeats that serve as protective caps that shorten with each cell division, a marker of aging. CMs are a known exception in which telomeres remain relatively stable throughout life in healthy individuals. We found that, relative to healthy controls, telomeres are significantly shorter in CMs of genetic HCM and DCM patient tissues harboring pathogenic mutations: TNNI3, MYBPC3, MYH7, DMD, TNNT2, and TTN Quantitative FISH (Q-FISH) of single cells revealed that telomeres were significantly reduced by 26% in HCM and 40% in DCM patient CMs in fixed tissue sections compared with CMs from age- and sex-matched healthy controls. In the cardiac tissues of the same patients, telomere shortening was not evident in vascular smooth muscle cells that do not express or require the contractile proteins, an important control. Telomere shortening was recapitulated in DCM and HCM CMs differentiated from patient-derived human-induced pluripotent stem cells (hiPSCs) measured by two independent assays. This study reveals telomere shortening as a hallmark of genetic HCM and DCM and demonstrates that this shortening can be modeled in vitro by using the hiPSC platform, enabling drug discovery.

Published
2018

28. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

Author

Behin, Anthony, Boentert, Matthias, Carvalho, Gerson, Chahin, Nizar, Charrow, Joel, Deegan, Patrick, Durmus Tekce, Hacer, Duval, Fanny, Genge, Angela, Gutmann, Ludwig, Henderson, Robert D, Hennermann, Julia B, Hiwot, Tarekegn, Hughes, Derralynn, Karaa, Amel, Karam, Chafic, Kautzky-Willer, Alexandra, Komaki, Hirofumi, Laforet, Pascal, Longo, Nicola, Malinova, Vera, Maré, Ricardo, Maxit, Clarisa, Mengel, Eugen, Moggio, Maurizio Gualtiero, Molnár, Mária Judit, Mongini, Tiziana Enrica, Nadaj-Pakleza, Aleksandra, Nascimento Osorio, Andres, Noury, Jean-Baptiste, Oliveira, Acary Souza Bulle, Parman, Yesim, Pena, Loren, Remiche, Gauthier, Sciacco, Monica, Shieh, Perry B, Smith, Cheryl, Stulnig, Thomas, Taithe, Frederic, Tard, Céline, Tarnopolsky, Mark, Vorgerd, Matthias, Whitley, Chester, Young, Peter, Alonso-Pérez, Jorge, Altemus, Patricia, Aubé-Nathier, Anne-Catherine, Avelar, Jennifer B, Bailey, Carrie, Bekircan-Kurt, Can Ebru, Billy, Jenny, Boschi, Silvia, Brown, Kathryn E, Carrera Garcia, Laura, Chase, Lauren, Cirne, Hamilton, Danjoux, Loïc, Davion, Jean-Baptiste, DeArmey, Stephanie, Fedotova, Ekaterina, Gandolfo, Eve, Grosz, Zoltan, Guellec, Dewi, Guettsches, Anne-Katrin, Guglieri, Michela, Hatcher, Erin, Helms, Sina, Hufgard-Leitner, Miriam, Klyushnikov, Sergey A., Langton, Jacqui, Linková, Lenka, Mavroudakis, Nicolas, Mazurová, Stella, Mori, Madoka, Müller-Miny, Louisa, Musumeci, Olimpia, Nance, Christopher S, Natera-de Benito, Daniel, Neel, Robert, Niizawa, Gabriela A, Noll, Lauren, Ortega, Erik, Pasnoor, Mamatha, Pautot, Vivien, Potulska-Chromik, Anna, Pugliese, Alessia, Questienne, Claire, Ramos Lopes, Margarida, Reyes-Leiva, David, Riedl, Michaela, Rugiero, Marcelo Francisco, Salort-Campana, Emmanuelle, Sgobbi Souza, Paulo Victor, Sole, Guilhem, Solera, Luca, Souto Lopes, Suzara, Specht, Sabine, Statland, Jeffrey, Swenson, Andrea, Tan, Chong Yew, Tizon, Sónia, van der Beek, N A M E, van Kooten, Harmke A., Wencel, Marie, Wenninger, Stephan, Zagnoli, Fabien, Diaz-Manera, Jordi, Kishnani, Priya S, Kushlaf, Hani, Ladha, Shafeeq, Mozaffar, Tahseen, Straub, Volker, Toscano, Antonio, van der Ploeg, Ans T, Berger, Kenneth I, Clemens, Paula R, Chien, Yin-Hsiu, Day, John W, Illarioshkin, Sergey, Roberts, Mark, Attarian, Shahram, Borges, Joao Lindolfo, Bouhour, Francoise, Choi, Young Chul, Erdem-Ozdamar, Sevim, Goker-Alpan, Ozlem, Kostera-Pruszczyk, Anna, Haack, Kristina An, Hug, Christopher, Huynh-Ba, Olivier, Johnson, Judith, Thibault, Nathan, Zhou, Tianyue, Dimachkie, Mazen M, and Schoser, Benedikt

Published
2021
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29. Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry

Author

Servais, Laurent, primary, Day, John W., additional, De Vivo, Darryl C., additional, Kirschner, Janbernd, additional, Mercuri, Eugenio, additional, Muntoni, Francesco, additional, Proud, Crystal M., additional, Shieh, Perry B., additional, Tizzano, Eduardo F., additional, Quijano-Roy, Susana, additional, Desguerre, Isabelle, additional, Saito, Kayoko, additional, Faulkner, Eric, additional, Benguerba, Kamal M., additional, Raju, Dheeraj, additional, LaMarca, Nicole, additional, Sun, Rui, additional, Anderson, Frederick A., additional, and Finkel, Richard S., additional

Published
2024
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30. Rasch Analysis of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales Administered to Patients With Duchenne Muscular Dystrophy

Author

Vishwanathan, V., Chidambaranathan, S., Biggar, W. Douglas, McAdam, Laura C., Mah, Jean K., Tulinius, Mar, Cnaan, Avital, Morgenroth, Lauren P., Leshner, Robert, TesiRocha, Carolina, Thangarajh, Mathula, Duong, Tina, Kornberg, Andrew, Ryan, Monique, Nevo, Yoram, Dubrovsky, Alberto, Clemens, Paula R., Abdel-Hamid, Hoda, Connolly, Anne M., Pestronk, Alan, Teasley, Jean, Bertorini, Tulio E., Webster, Richard, Kolski, Hanna, Kuntz, Nancy, Driscoll, Sherilyn, Bodensteiner, John B., Carlo, Jose, Gorni, Ksenija, Lotze, Timothy, Day, John W., Karachunski, Peter, Henricson, Erik K., Abresch, Richard T., Joyce, Nanette C., McDonald, Craig M., Landfeldt, Erik, Iff, Joel, and Henricson, Erik

Published
2021
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31. Miyoshi myopathy and limb girdle muscular dystrophy R2 are the same disease

Author

Moore, Ursula, Gordish, Heather, Diaz-Manera, Jordi, James, Meredith K., Mayhew, Anna G., Guglieri, Michela, Fernandez-Torron, Roberto, Rufibach, Laura E., Feng, Jia, Blamire, Andrew M., Carlier, Pierre G., Spuler, Simone, Day, John W., Jones, Kristi J., Bharucha-Goebel, Diana X., Salort-Campana, Emmanuelle, Pestronk, Alan, Walter, Maggie C., Paradas, Carmen, Stojkovic, Tanya, Mori-Yoshimura, Madoka, Bravver, Elena, Pegoraro, Elena, Lowes, Linda Pax, Mendell, Jerry R., Bushby, Kate, and Straub, Volker

Published
2021
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32. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial

Author

Day, John W, Finkel, Richard S, Chiriboga, Claudia A, Connolly, Anne M, Crawford, Thomas O, Darras, Basil T, Iannaccone, Susan T, Kuntz, Nancy L, Peña, Loren D M, Shieh, Perry B, Smith, Edward C, Kwon, Jennifer M, Zaidman, Craig M, Schultz, Meredith, Feltner, Douglas E, Tauscher-Wisniewski, Sitra, Ouyang, Haojun, Chand, Deepa H, Sproule, Douglas M, Macek, Thomas A, and Mendell, Jerry R

Published
2021
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33. Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study

Author

Rudnicki, Stacy A., Andrews, Jinsy A., Duong, Tina, Cockroft, Bettina M., Malik, Fady I., Meng, Lisa, Wei, Jenny, Wolff, Andrew A., Genge, Angela, Johnson, Nicholas E., Tesi-Rocha, Carolina, Connolly, Anne M., Darras, Basil T., Felice, Kevin, Finkel, Richard S., Shieh, Perry B., Mah, Jean K., Statland, Jeffrey, Campbell, Craig, Habib, Ali A., Kuntz, Nancy L., Oskoui, Maryam, and Day, John W.

Published
2021
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42. Assessing the Assisted Six-Minute Cycling Test as a Measure of Endurance in Non-Ambulatory Patients with Spinal Muscular Atrophy (SMA)

Author

Tang, Whitney J., primary, Gu, Bo, additional, Montalvo, Samuel, additional, Dunaway Young, Sally, additional, Parker, Dana M., additional, de Monts, Constance, additional, Ataide, Paxton, additional, Ni Ghiollagain, Noirin, additional, Wheeler, Matthew T., additional, Tesi Rocha, Carolina, additional, Christle, Jeffrey W., additional, He, Zihuai, additional, Day, John W., additional, and Duong, Tina, additional

Published
2023
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43. Sunfish parts 1 and 2: 4-year efficacy and safety data of risdiplam in types 2 and 3 spinal muscular atrophy (SMA)

Author

Oskoui, Maryam, primary, Deconinck, Nicolas, additional, Mazzone, Elena S., additional, Nascimento, Andres, additional, Day, John W., additional, Saito, Kayoko, additional, Vuillerot, Carole, additional, Baranello, Giovanni, additional, Boespflug-Tanguy, Odile, additional, Goemans, Nathalie, additional, Kirschner, Janbernd, additional, Kostera-Pruszczyk, Anna, additional, Servais, Laurent, additional, Braid, Jessica, additional, Gerber, Marianne, additional, Gorni, Ksenija, additional, Martin, Carmen, additional, Yeung, Wai Yin, additional, Scalco, Renata S., additional, and Mercuri, Eugenio, additional

Published
2023
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44. Cerebrospinal Fluid Proteomic Changes after Nusinersen in Patients with Spinal Muscular Atrophy

Author

Beaudin, Marie, primary, Kamali, Tahereh, additional, Tang, Whitney, additional, Hagerman, Katharine A., additional, Dunaway Young, Sally, additional, Ghiglieri, Lisa, additional, Parker, Dana M., additional, Lehallier, Benoit, additional, Tesi-Rocha, Carolina, additional, Sampson, Jacinda B., additional, Duong, Tina, additional, and Day, John W., additional

Published
2023
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47. Disease Trajectories in the Revised Hammersmith Scale in a Cohort of Untreated Patients with Spinal Muscular Atrophy types 2 and 3

Author

Wolfe, Amy, Stimpson, Georgia, Ramsey, Danielle, Coratti, Giorgia, Dunaway Young, Sally, Mayhew, Anna, Pane, Marika, Rohwer, Annemarie, Muni Lofra, Robert, Duong, Tina, O’Reilly, Emer, Milev, Evelin, Civitello, Matthew, Sansone, Valeria A., D’Amico, Adele, Bertini, Enrico, Messina, Sonia, Bruno, Claudio, Albamonte, Emilio, Mazzone, Elena, Main, Marion, Montes, Jacqueline, Glanzman, Allan M., Zolkipli-Cunningham, Zarazuela, Pasternak, Amy, Marini-Bettolo, Chiara, Day, John W., Darras, Basil T., De Vivo, Darryl C., Baranello, Giovanni, Scoto, Mariacristina, Finkel, Richard S., Mercuri, Eugenio, and Muntoni, Francesco

Abstract

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by progressive motor function decline. Motor function is assessed using several functional outcome measures including the Revised Hammersmith Scale (RHS). In this study, we present longitudinal trajectories for the RHS in an international cohort of 149 untreated paediatric SMA 2 and 3 patients (across 531 assessments collected between March 2015 and July 2019). We contextualise these trajectories using both the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM). At baseline, this cohort included 50% females and 15% of patients had undergone spinal fusion surgery. Patient trajectories were modelled using a natural cubic spline with age, sex, and random effects for each patient. RHS and HFMSE scores show similar trends over time in this cohort not receiving disease modifying therapies. The results confirm the strong correlation between the RHS and RULM previously observed in SMA types 2 and 3a. Scoliosis surgery is associated with a reduction of 3 points in the RHS, 4.5 points in the HFMSE for the SMA 2 population, and a reduction of 11.8 points in the RHS, and 13.4 points in the HFMSE for the SMA 3a populations. When comparing the RHS and RULM, there is a lower correlation in the type 3a’s than the type 2 patients. In the SMA 2 population, there is no significant difference between the sexes in either the RHS or HFMSE trajectories. There is no significant difference in the RULM trajectory in the SMA 2 or 3a participants by sex. This study demonstrates that the RHS could be used in conjunction with other functional measures such as the RULM to holistically detect SMA disease progression. This will assist with fully understanding changes that occur with treatments, further defining trajectories and therapy outcomes.

Published
2024
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48. Nusinersen Treatment in Adults with Spinal Muscular Atrophy

Author

Duong, Tina, Wolford, Connie, McDermott, Michael P., Macpherson, Chelsea E., Pasternak, Amy, Glanzman, Allan M., Martens, William B., Kichula, Elizabeth, Darras, Basil T., De Vivo, Darryl C., Zolkipli-Cunningham, Zarazuela, Finkel, Richard S., Zeineh, Michael, Wintermark, Max, Sampson, Jacinda, Hagerman, Katharine A., Young, Sally Dunaway, and Day, John W.

Published
2021
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