Review
Clinical Neurology
W. Douglas Biggar, Andrew Skalsky, Craig M. McDonald
Summary: Deflazacort and prednisone/prednisolone are both effective in improving muscle strength, delaying disease progression, and improving pulmonary function in patients with Duchenne muscular dystrophy (DMD). However, deflazacort may have fewer side effects in terms of weight gain and behavior compared to prednisone/prednisolone, although it may have a negative impact on bone health, growth parameters, and cataracts. Evidence suggests that deflazacort and prednisone/prednisolone have similar or slower rates of functional decline in DMD patients.
JOURNAL OF NEUROMUSCULAR DISEASES
(2022)
Article
Genetics & Heredity
Georgia Stimpson, Sarah Raquq, Mary Chesshyre, Mary Fewtrell, Deborah Ridout, Anna Sarkozy, Adnan Manzur, Vandana Ayyar Gupta, Ramona De Amicis, Francesco Muntoni, Giovanni Baranello
Summary: The objective of this study was to analyze growth data (weight, height, and BMI) in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD) using retrospective, observational, longitudinal data. The study considered glucocorticoids use, dystrophin isoforms, amenability to exon skipping drug subgroups, and the impact of growth on loss of ambulation. The results showed that boys in the daily regime subgroups had slower yearly height growth compared to those who were not treated. Boys with affected expression of certain dystrophin isoforms were shorter than those with unaffected expression. Increased weight was not associated with earlier loss of ambulation, but taller boys at the age of 10-11 years were more at risk of losing ambulation.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Grace Liu, Philip Lipari, Anna Mollin, Stephen Jung, Irina Teplova, Wencheng Li, Lanqing Ying, Vijay More, William Lennox, Shirley Yeh, Eric McGann, Young-Choon Moon, Cari Rice, Eduardo Huarte, Barbara Gruszka, Balmiki Ray, Elizabeth Goodwin, Patricia Buckendahl, Edward Yurkow, Bruce Braughton, Jana Narasimhan, Ellen Welch, Gregory Voronin, Marla Weetall
Summary: DMD is a genetic disease that leads to gradual muscle loss, and deflazacort is the FDA-approved standard treatment for DMD, while vamorolone is a novel corticosteroid being investigated. We compared the pharmaceutical properties, efficacy, and safety of these three drugs in a mouse model. The study found that vamorolone and other corticosteroids had similar side effects at effective doses, and vamorolone had a higher risk of CNS side effects due to its distribution in the brain.
HUMAN MOLECULAR GENETICS
(2023)
Review
Health Care Sciences & Services
Jessica R. Marden, Claudio Santos, Brian Pfister, Richard Able, Henry Lane, Michael Somma, Jing Zhao, James Signorovitch, Julie Parsons, Susan Apkon
Summary: The aim of the study was to describe reasons for switching from prednisone/prednisolone to deflazacort and associated clinical outcomes among patients with DMD and BMD in the USA. The primary reasons for switching were to slow disease progression and tolerability, with 90-95% of patients finding deflazacort effective in addressing these reasons.
JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
(2021)
Article
Health Care Sciences & Services
Perry B. Shieh, Gary Elfring, Panayiota Trifillis, Claudio Santos, Stuart W. Peltz, Julie A. Parsons, Susan Apkon, Basil T. Darras, Craig Campbell, Craig M. McDonald
Summary: In this study, deflazacort was found to provide clinically meaningful delays in loss of physical milestones over 48 weeks compared with prednisone/prednisolone for patients with nonsense mutation Duchenne muscular dystrophy. Significant improvements in 6-min walk distance and timed function tests were observed with deflazacort, especially in stair climbing and descending.
JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
(2021)
Article
Biology
Rodrigo Martins Dias, Rosangela Akemi Hoshi, Luiz Carlos Marques Vanderlei, Carlos Bandeira de Mello Monteiro, Mayra Priscila Boscolo Alvarez, Tania Brusque Crocetta, Luis Fernando Grossklauss, Deborah Cristina Goncalves Luiz Fernani, Maria Tereza Artero Prado Dantas, Fabiana Paula Almeida Martins, David M. Garner, Luiz Carlos Abreu, Celso Ferreira, Talita Dias da Silva
Summary: The study found that individuals with Duchenne Muscular Dystrophy (DMD) receiving Prednisolone therapy showed cardiac autonomic function comparable to the typically developed control group, while those receiving Deflazacort therapy had lower cardiac autonomic function. Corticosteroids have the potential to affect the cardiac autonomic modulation in adolescents with DMD, with Prednisone/Prednisolone promoting improved responses in sympathovagal activity compared to Deflazacort.
Article
Medicine, General & Internal
Michela Guglieri, Kate Bushby, Michael P. McDermott, Kimberly A. Hart, Rabi Tawil, William B. Martens, Barbara E. Herr, Elaine McColl, Chris Speed, Jennifer Wilkinson, Janbernd Kirschner, Wendy M. King, Michelle Eagle, Mary W. Brown, Tracey Willis, Robert C. Griggs
Summary: A double-blind, parallel-group randomized clinical trial was conducted to compare the efficacy and adverse effects of different corticosteroid regimens in boys with Duchenne muscular dystrophy. The study found that daily prednisone and daily deflazacort were more effective than intermittent prednisone for improving motor function, pulmonary function, and satisfaction with treatment over a 3-year period. There was no significant difference between the two daily corticosteroid regimens.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Health Care Sciences & Services
Brenda L. Wong, Tiffany Cook, Hawken Miller
Summary: This summary is about the Cincinnati study on Duchenne muscular dystrophy (DMD). The study analyzed the data of 435 male patients with DMD who were treated at the Cincinnati Children's Hospital Medical Center. The results showed that patients who took deflazacort had a later onset of wheelchair use and a lower risk of scoliosis compared to those who took prednisone.
JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
(2022)
Article
Veterinary Sciences
Ricardo Videla, Carla Sommardahl, Joe Smith, Deanna M. W. Schaefer, Sherry Cox
Summary: This study investigated the pharmacokinetics of prednisolone in healthy adult alpacas after intravenous and oral administration. The results showed that the serum concentrations of prednisolone were similar to other veterinary species after IV and PO administration. However, oral administration led to changes in blood parameters and bioavailability was determined to be 13.7%. Further research is needed to determine the pharmacodynamics of prednisolone in alpacas.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Health Care Sciences & Services
Craig M. McDonald, Jessica R. Marden, Perry B. Shieh, Brenda L. Wong, Henry Lane, Adina Zhang, Ha Nguyen, Molly Frean, Panayiota Trifillis, Karyn Koladicz, James Signorovitch
Summary: This study found that daily deflazacort had greater benefits than daily prednisone, particularly among older patients with more advanced disease progression.
JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
(2023)
Article
Neurosciences
Susan Sienko, Cathleen E. Buckon, Anita Bagley, Loretta Staudt, Eileen Fowler, Kent Heberer, Mitell Sison-Williamson, Craig McDonald, Michael D. Sussman
Summary: In boys with DMD, walking energy cost increased over time as velocity decreased. Both NNcost and SMC-EC were identified as appropriate normalization schemes for the longitudinal assessment of energy cost in boys with DMD, showing similar sensitivity to age and differences in sensitivity to changes in height over time.
Article
Clinical Neurology
Giulio Gadaleta, Guido Urbano, Chiara Brusa, Rossella D'Alessandro, Enrica Rolle, Ilaria Cavallina, Alessio Mattei, Fulvia Ribolla, Claudia Raineri, Stefano Pidello, Liliana Vercelli, Federica S. Ricci, Tiziana E. Mongini
Summary: The clinical characteristics of adults with DMD include mechanical ventilation, swallowing and nutritional issues, and bone density alterations. Other issues include respiratory infections, gastrointestinal symptoms, metabolic acidosis, psychiatric symptoms, and chronic pain. Patients have a negative perception of their physical health but a more positive assessment of their mental health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Pediatrics
Yan-li Ma, Wei-hua Zhang, Guo-hong Chen, Li-fang Song, Yuan Wang, Rui-li Yuan, Ying Wang, Xiu-yong Cheng
Summary: This study aims to explore the potential of combining walking alone milestone with the reading-frame rule for early diagnosis of Duchenne muscular dystrophy (DMD). The results showed that the combined method significantly improved the early diagnosis rate of DMD.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biotechnology & Applied Microbiology
Prashant Monian, Chikdu Shivalila, Genliang Lu, Mamoru Shimizu, David Boulay, Karley Bussow, Michael Byrne, Adam Bezigian, Arindom Chatterjee, David Chew, Jigar Desai, Frank Favaloro, Jack Godfrey, Andrew Hoss, Naoki Iwamoto, Tomomi Kawamoto, Jayakanthan Kumarasamy, Anthony Lamattina, Amber Lindsey, Fangjun Liu, Richard Looby, Subramanian Marappan, Jake Metterville, Ronelle Murphy, Jeff Rossi, Tom Pu, Bijay Bhattarai, Stephany Standley, Snehlata Tripathi, Hailin Yang, Yuan Yin, Hui Yu, Cong Zhou, Luciano H. Apponi, Pachamuthu Kandasamy, Chandra Vargeese
Summary: The study describes chemically modified oligonucleotides called AIMers that can efficiently and specifically direct RNA-editing enzymes to edit endogenous transcripts. Fully chemically modified AIMers with chimeric backbones showed enhanced potency and editing efficiency compared to uniformly modified AIMers in vitro. In vivo, AIMers targeted to hepatocytes achieved significant editing without off-target effects in non-human primate liver. This study demonstrates the potential of AIMers for therapeutic applications.
NATURE BIOTECHNOLOGY
(2022)
Article
Medicine, Research & Experimental
Cedric Happi Mbakam, Joel Rousseau, Yaoyao Lu, Anne Bigot, Kamel Mamchaoui, Vincent Mouly, Jacques P. Tremblay
Summary: In this study, researchers used CRISPR-Cas9 prime editing technology to correct a mutation in the DMD gene, resulting in improved editing efficiency and restoration of dystrophin protein expression. Optimization of the reverse transcription template sequence led to a significant increase in the editing percentage of the target nucleotide.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Letter
Clinical Neurology
H. Argente-Escrig, D. Schultheis, L. Kamm, M. Schowalter, C. Thiel, M. Tuerk, C. S. Clemen, N. Muelas, M. J. Castanon, G. Wiche, H. Herrmann, J. J. Vilchez, R. Schroeder
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Marina Frasquet, Ricard Rojas-Garcia, Herminia Argente-Escrig, Juan Francisco Vazquez-Costa, Nuria Muelas, Juan Jesus Vilchez, Rafael Sivera, Elvira Millet, Marisa Barreiro, Jordi Diaz-Manera, Janina Turon-Sans, Elena Cortes-Vicente, Luis Querol, Laura Ramirez-Jimenez, Dolores Martinez-Rubio, Ana Sanchez-Monteagudo, Carmen Espinos, Teresa Sevilla, Vincenzo Lupo
Summary: This study confirms the genetic heterogeneity of distal hereditary motor neuropathies and establishes biallelic SORD mutations as a cause of the disease in different populations. The study also reveals the genetic diagnostic rate, most common genetic mutations, and prevalence of the disease.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Nuria Muelas, Marina Frasquet, Fernando Mas-Estelles, Pilar Marti, Laura Martinez-Vicente, Teresa Sevilla, Inmaculada Azorin, Javier Poyatos-Garcia, Herminia Argente-Escrig, Roger Vilchez, Juan F. Vazquez-Costa, Luis Bataller, Juan J. Vilchez
Summary: Laing myopathy exhibits broad clinical and pathological variability, with muscle imaging profiles providing valuable insights and imaging analysis validated as an outcome measure. Various imaging features are correlated with age at onset, disease duration, and clinical manifestations, demonstrating the usefulness of imaging analysis in categorizing patients and monitoring disease progression over time.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Jorge Alonso-Perez, Lidia Gonzalez-Quereda, Claudio Bruno, Chiara Panicucci, Afagh Alavi, Shahriar Nafissi, Yalda Nilipour, Edmar Zanoteli, Lucas Michielon de Augusto Isihi, Bela Melegh, Kinga Hadzsiev, Nuria Muelas, Juan J. Vilchez, Mario Emilio Dourado, Naz Kadem, Gultekin Kutluk, Muhammad Umair, Muhammad Younus, Elena Pegorano, Luca Bello, Thomas O. Crawford, Xavier Suarez-Calvet, Ana Topf, Michela Guglieri, Chiara Marini-Bettolo, Pia Gallano, Volker Straub, Jordi Diaz-Manera
Summary: Sarcoglycanopathies are a group of genetic muscular diseases, with delta-sarcoglycanopathy being the rarest subtype. This study retrospectively analyzed a large cohort of delta-sarcoglycanopathy patients and found that the disease is severe and rapidly progressive, predominantly affecting limb muscles. Similar to other forms of sarcoglycanopathies, the abundance of protein on muscle biopsy inversely correlates with disease severity and progression rate.
Article
Clinical Neurology
Rafael Sivera, Vincenzo Lupo, Marina Frasquet, Herminia Argente-Escrig, Jorge Alonso-Perez, Jordi Diaz-Manera, Luis Querol, Maria del Mar Garcia-Romero, Samuel Ignacio Pascual, Tania Garcia-Sobrino, Carmen Paradas, Juan Francisco Vazquez-Costa, Nuria Muelas, Elvira Millet, Juan Jesus Vilchez, Carmen Espinos, Teresa Sevilla
Summary: This study identified 15 patients with CMT2Z caused by MORC2 mutations in Spain, with most exhibiting a scapuloperoneal phenotype and a few showing a neurodevelopmental phenotype. The findings suggest a diverse spectrum of disease characteristics and clinical presentations.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Medicine, Research & Experimental
Maria Sabater-Arcis, Ariadna Bargiela, Nerea Moreno, Javier Poyatos-Garcia, Juan J. Vilchez, Ruben Artero
Summary: This study identified that the upregulation of RNA-binding protein MSI2 in myotonic dystrophy type 1 (DM1) patients leads to repression of miR-7, excessive autophagy, and muscle wasting. By using gene-silencing and small molecule inhibitors, reducing MSI2 levels or activity can increase miR-7 expression, suppress autophagy, and downregulate genes related to muscle atrophy. This suggests MSI2 as a potential therapeutic target for treating muscle dysfunction in DM1.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Editorial Material
Clinical Neurology
Juan Jesus Vilchez Padilla
JOURNAL OF NEUROMUSCULAR DISEASES
(2021)
Review
Genetics & Heredity
Juan Luque, Ingrid Mendes, Beatriz Gomez, Beatriz Morte, Miguel Lopez de Heredia, Enrique Herreras, Virginia Corrochano, Juan Bueren, Pia Gallano, Rafael Artuch, Cristina Fillat, Luis A. Perez-Jurado, Lluis Montoliu, Angel Carracedo, Jose M. Millan, Susan M. Webb, Francesc Palau, Pablo Lapunzina
Summary: CIBERER, a thematic area of CIBER, focuses on rare disease research. It aims to facilitate collaboration between biomedical and clinical research groups and provide new tools for the diagnosis and therapy of low-prevalence diseases.
Article
Genetics & Heredity
Ana Victoria Marco-Hernandez, Miguel Tomas-Vila, Alejandro Montoya-Filardi, Honorio Barranco-Gonzalez, Juan Jesus Vilchez Padilla, Inmaculada Azorin, Patricia Smeyers Dura, Sandra Monfort-Membrado, Inmaculada Pitarch-Castellano, Francisco Martinez-Castellano
Summary: The IMMT gene codes for mitofilin, a protein that regulates mitochondrial cristae morphology, and mutations in this gene may lead to alterations in mitochondrial structure and function. Two patients from a family with developmental encephalopathy and optic neuropathy were found to have a likely pathogenic homozygous variant in the IMMT gene, which is associated with abnormal mitochondrial cristae observed by electron microscopy.
Article
Clinical Neurology
Raquel Baviera-Munoz, Marina Campins-Romeu, Lidon Carretero-Vilarroig, Isabel Sastre-Bataller, Irene Martinez-Torres, Juan F. Vazquez-Costa, Nuria Muelas, Teresa Sevilla, Juan J. Vilchez, Elena Aller, Teresa Jaijo, Luis Bataller, Carmen Espinos
Summary: Spastic ataxia is the most common phenotype found in Spanish SPG7 patients, with other phenotypes including pure spastic paraplegia and complex phenotypes. The most frequent pathogenic variant encountered was p.Ala510Val, and two novel variants were also found.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Health Care Sciences & Services
Perry B. Shieh, Gary Elfring, Panayiota Trifillis, Claudio Santos, Stuart W. Peltz, Julie A. Parsons, Susan Apkon, Basil T. Darras, Craig Campbell, Craig M. McDonald
Summary: In this study, deflazacort was found to provide clinically meaningful delays in loss of physical milestones over 48 weeks compared with prednisone/prednisolone for patients with nonsense mutation Duchenne muscular dystrophy. Significant improvements in 6-min walk distance and timed function tests were observed with deflazacort, especially in stair climbing and descending.
JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
(2021)
Article
Clinical Neurology
Jeffrey M. Statland, Craig Campbell, Urvi Desai, Chafic Karam, Jordi Diaz-Manera, Jeffrey T. Guptill, Lawrence Korngut, Angela Genge, Rabi N. Tawil, Lauren Elman, Nanette C. Joyce, Kathryn R. Wagner, Georgios Manousakis, Anthony A. Amato, Russell J. Butterfield, Perry B. Shieh, Matthew Wicklund, Josep Gamez, Cynthia Bodkin, Alan Pestronk, Conrad C. Weihl, Juan J. Vilchez-Padilla, Nicholas E. Johnson, Katherine D. Mathews, Barry Miller, Ashley Leneus, Marcie Fowler, Marc van de Rijn, Kenneth M. Attie
Summary: This study evaluated the safety and efficacy of ACE-083 in treating FSHD. The results showed that ACE-083 can increase muscle volume, but did not lead to consistent improvements in functional outcomes or patient-reported outcomes.
Article
Clinical Neurology
Herminia Argente-Escrig, Juan J. Vilchez, Marina Frasquet, Nuria Muelas, Inmaculada Azorin, Roger Vilchez, Elvira Millet-Sancho, Inmaculada Pitarch, Miguel Tomas-Vila, Juan F. Vazquez-Costa, Fernando Mas-Estelles, Clara Marco-Marin, Carmen Espinos, Pablo Serrano-Lorenzo, Miguel A. Martin, Vincenzo Lupo, Teresa Sevilla
Summary: Three patients with infantile-onset demyelinating neuropathy showed intellectual disability, cerebellar abnormalities, and severe demyelinating neuropathy, all carrying compound heterozygous variants of the TRMT5 gene.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Cell Biology
Francisco Diez-Fuertes, Maria Rosa Lopez-Huertas, Javier Garcia-Perez, Esther Calonge, Mercedes Bermejo, Elena Mateos, Pilar Marti, Nuria Muelas, Juan Jesus Vilchez, Mayte Coiras, Jose Alcami, Sara Rodriguez-Mora
Summary: LGMDD2 is a rare form of muscular dystrophy characterized by the addition of a 15-amino acid tail in the C-terminus of the TNPO3 gene. The study found that LGMDD2 patients exhibit a pro-inflammatory state, with alterations in IL-17 signaling pathway and increased activity of metallopeptidases and TNF response. Additionally, LGMDD2 patients have elevated levels of interferons and inflammatory mediators, suggesting an antiviral environment and resistance to HIV-1 infection, but potentially impairing muscular function and worsening disease progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Clinical Neurology
Michela Guglieri, Paula R. Clemens, Seth J. Perlman, Edward C. Smith, Iain Horrocks, Richard S. Finkel, Jean K. Mah, Nicolas Deconinck, Nathalie Goemans, Jana Haberlova, Volker Straub, Laurel J. Mengle-Gaw, Benjamin D. Schwartz, Amy D. Harper, Perry B. Shieh, Liesbeth De Waele, Diana Castro, Michelle L. Yang, Monique M. Ryan, Craig M. McDonald, Mar Tulinius, Richard Webster, Hugh J. McMillan, Nancy L. Kuntz, Vashmi K. Rao, Giovanni Baranello, Stefan Spinty, Anne-Marie Childs, Annie M. Sbrocchi, Kathryn A. Selby, Migvis Monduy, Yoram Nevo, Juan J. Vilchez-Padilla, Andres Nascimento-Osorio, Erik H. Niks, Imelda J. M. de Groot, Marina Katsalouli, Meredith K. James, Johannes van den Anker, Jesse M. Damsker, Alexandra Ahmet, Leanne M. Ward, Mark Jaros, Phil Shale, Utkarsh J. Dang, Eric P. Hoffman
Summary: This study aimed to investigate the efficacy and safety of a novel corticosteroidal anti-inflammatory drug called vamorolone in boys with Duchenne muscular dystrophy (DMD). The results showed that vamorolone demonstrated comparable efficacy to prednisone but with better safety profile over a 24-week treatment period, with less impact on growth and bone metabolism.
