Article
Pharmacology & Pharmacy
Zeren Sun, Dengqiu Xu, Lei Zhao, Xihua Li, Sijia Li, Xiaofei Huang, Chunjie Li, Lixin Sun, Bing Liu, Zhenzhou Jiang, Luyong Zhang
Summary: The study found that fenofibrate can promote the differentiation of myofibers by down-regulating the expression of myostatin protein in myoblasts, significantly improving muscle function and reducing muscle damage in mdx mice, along with anti-inflammatory effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Cell Biology
Tue L. Nielsen, John Vissing, Thomas O. Krag
Summary: While preclinical studies have shown potential for increasing muscle mass and improving the pathological features of muscle diseases by inhibiting myostatin, there has been a lack of successful translation of these results into clinical trials with patient populations.
Article
Multidisciplinary Sciences
Hiroyasu Muramatsu, Taichi Kuramochi, Hitoshi Katada, Atsunori Ueyama, Yoshinao Ruike, Ken Ohmine, Meiri Shida-Kawazoe, Rie Miyano-Nishizawa, Yuichiro Shimizu, Momoko Okuda, Yuji Hori, Madoka Hayashi, Kenta Haraya, Nobuhiro Ban, Tatsuya Nonaka, Masaki Honda, Hidetomo Kitamura, Kunihiro Hattori, Takehisa Kitazawa, Tomoyuki Igawa, Yoshiki Kawabe, Junichi Nezu
Summary: This study introduces a novel antibody therapeutic approach targeting myostatin, which shows superior muscle strength-improvement effects in mouse disease models and normal cynomolgus monkeys. The effectiveness of GYM329 is attributed to its myostatin specificity and sweeping capability, indicating its potential in improving muscle strength in patients with muscular disorders.
SCIENTIFIC REPORTS
(2021)
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)
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
Geriatrics & Gerontology
Brenda L. Wong, Suzanne Summer, Paul S. Horn, Meilan M. Rutter, Irina Rybalsky, Cuixia Tian, Karen C. Shellenbarger, Heidi J. Kalkwarf
Summary: Mutations in the dystrophin gene result in varying clinical severity of DMD, and certain indices such as ALM and ALMI may serve as potential markers for evaluating the severity of the disease and informing clinical care decisions and trial designs.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Endocrinology & Metabolism
Leanne M. Ward, Anup Choudhury, Nathalie Alos, David A. Cabral, Celia Rodd, Anne Marie Sbrocchi, Shayne Taback, Raja Padidela, Nick J. Shaw, Eva Hosszu, Mikhail Kostik, Ekaterina Alexeeva, Kebashni Thandrayen, Nazih Shenouda, Jacob L. Jaremko, Gangadhar Sunkara, Sarfaraz Sayyed, R. Paul Aftring, Craig F. Munns
Summary: In this study, children with GIO who received intravenous zoledronic acid (ZA) showed a significant increase in lumbar spine bone density z score (LSBMDZ) compared to those who received a placebo after 1 year of treatment. Most adverse events occurred after the first infusion.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Clinical Neurology
Craig M. Zaidman, Crystal M. Proud, Craig M. Mcdonald, Kelly J. Lehman, Natalie L. Goedeker, Stefanie Mason, Alexander P. Murphy, Maitea Guridi, Shufang Wang, Carol Reid, Eddie Darton, Christoph Wandel, Sarah Lewis, Jyoti Malhotra, Danielle A. Griffin, Rachael A. Potter, Louise R. Rodino-Klapac, Jerry R. Mendell
Summary: The study ENDEAVOR demonstrated that the commercial process delandistrogene moxeparvovec is safe and effective in improving micro-dystrophin expression in patients with Duchenne muscular dystrophy. After 12 weeks of treatment, significant improvements were observed in micro-dystrophin expression, as well as patient's functional outcomes and quality of life at 1 year.
ANNALS OF NEUROLOGY
(2023)
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.
Review
Cell Biology
Elisa Domi, Malvina Hoxha, Emanuela Prendi, Bruno Zappacosta
Summary: Duchenne muscular dystrophy is a muscular disease with no cure, and SIRT1 has been identified as a potential therapeutic target for the condition. Activation of SIRT1 improves muscle function, while its inhibition leads to muscle fragility.
Article
Biochemistry & Molecular Biology
Dong Kyung Sung, Hyeongseop Kim, Sang Eon Park, Jiwon Lee, Ju-A Kim, Young-Chul Park, Hong Bae Jeon, Jong Wook Chang, Jeehun Lee
Summary: This study demonstrated that oral administration of Lactobacillus casei expressing modified human myostatin (BLS-M22) can stimulate the production of sufficient myostatin-specific antibodies and improve the dystrophic features of a mouse model of Duchenne muscular dystrophy (mdx mouse). BLS-M22 treatment resulted in significantly increased levels of anti-myostatin IgG and decreased serum creatine kinase levels in mdx mice. It also improved body weight, motor function, and histological characteristics. The circulating antibodies generated after BLS-M22 administration successfully decreased serum myostatin concentration. Overall, the findings suggest the potential of BLS-M22 as a treatment for DMD, but further clinical trials are necessary to determine its efficacy and safety in humans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Krzysztof Zablocki, Dariusz C. Gorecki
Summary: Muscular dystrophies are inherited neuromuscular diseases that cause progressive disability and can reduce life expectancy. Loss of dystrophin or mutations in sarcoglycan-encoding genes lead to the loss of a-sarcoglycan ecto-ATPase activity, disrupting purinergic signaling and causing chronic inflammation in dystrophic muscles. Over-activation of P2X7 purinoceptors exacerbates pathology in dystrophic muscle cells. Blocking P2X7 receptors has shown promising results in mouse models and should be considered for the treatment of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Deng-qiu Xu, Lei Zhao, Si-jia Li, Xiao-fei Huang, Chun-jie Li, Li-xin Sun, Xi-hua Li, Lu-yong Zhang, Zhen-zhou Jiang
Summary: Catalpol can restore skeletal muscle strength and alleviate skeletal muscle damage in aged mdx mice, providing a potential novel therapy for DMD. Catalpol attenuates muscle fibrosis by inhibiting the TGF-beta 1/TAK1 signaling pathway.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Biochemistry & Molecular Biology
Silvia Consalvi, Luca Tucciarone, Elisa Macri, Marco De Bardi, Mario Picozza, Illari Salvatori, Alessandra Renzini, Sergio Valente, Antonello Mai, Viviana Moresi, Pier Lorenzo Puri
Summary: Late-stage mdx FAPs exhibit abnormal HDAC activity and genome-wide alterations of histone acetylation that cannot be fully reversed by HDACi. HDACi show general resistance in inducing H3K9/14 hyperacetylation in late-stage mdx FAPs, but is effective in reducing promoter acetylation and blunting SASP gene activation.
Article
Multidisciplinary Sciences
Michael Ziemba, Molly Barkhouse, Kitipong Uaesoontrachoon, Mamta Giri, Yetrib Hathout, Utkarsh J. Dang, Heather Gordish-Dressman, Kanneboyina Nagaraju, Eric P. Hoffman
Summary: Duchenne muscular dystrophy is caused by dystrophin deficiency, leading to downstream pathophysiological pathways that drive disability. Dystrophin replacement strategies may trigger these pathways, so combination therapies targeting multiple downstream pathways are crucial. Blood biomarkers could be used to assess drug combinations for treating DMD in both mouse models and human studies.
Editorial Material
Clinical Neurology
Maryam Oskoui, Hernan Gonorazky, Hugh J. McMillan, James J. Dowling, Reshma Amin, Cynthia Gagnon, Kathryn Selby
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Kristina M. Joyal, Jessica MacGregor, Lamia M. Hayawi, Richard J. Webster, Hugh J. McMillan
Summary: This study reviewed the volume and referral sources of nerve conduction studies (NCS) and electromyography (EMG) at a pediatric tertiary care hospital from 2014 to 2019. The findings indicate that NCS/EMG remains a valuable diagnostic tool, especially for acquired neuromuscular conditions, and can be well tolerated in children of all ages without the need for sedation.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Letter
Clinical Neurology
Kristin D. Kernohan, Hugh J. McMillan, Ed Yeh, Melanie Lacaria, Michael Kowalski, Craig Campbell, James J. Dowling, Hernan Gonorazky, Janet Marcadier, Mark A. Tarnopolsky, Jiri Vajsar, Alex Mackenzie, Pranesh Chakraborty
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Hugh J. McMillan, Crystal M. Proud, Michelle A. Farrar, Ian E. Alexander, Francesco Muntoni, Laurent Servais
Summary: Gene therapy for spinal muscular atrophy (SMA) is a significant advancement in the treatment of neurologic diseases. Onasemnogene abeparvovec, a one-time gene replacement therapy, has shown improved survival and motor milestones for SMA patients. However, gene therapy is still in its early stages and faces challenges in transgene delivery.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
William J. Groh, Deepak Bhakta, Gordon F. Tomaselli, Ryan G. Aleong, Ricardo Alkmim Teixeira, Anthony Amato, Samuel J. Asirvatham, Yong-Mei Cha, Domenico Corrado, Denis Duboc, Zachary D. Goldberger, Minoru Horie, Joseph E. Hornyak, John Lynn Jefferies, Stefan Kaab, Jonathan M. Kalman, Naomi J. Kertesz, Neal K. Lakdawala, Pier D. Lambiase, Steven A. Lubitz, Hugh J. McMillan, Elizabeth M. McNally, Margherita Milone, Narayanan Namboodiri, Saman Nazarian, Kristen K. Patton, Vincenzo Russo, Frederic Sacher, Pasquale Santangeli, Win-Kuang Shen, Dario C. Sobral Filho, Bruce S. Stambler, Claudia Stollberger, Karim Wahbi, Xander H. T. Wehrens, Menachem Mendel Weiner, Matthew T. Wheeler, Katja Zeppenfeld
Summary: This document provides guidance for healthcare professionals in caring for patients with arrhythmic complications of neuromuscular disorders. It presents an overview of arrhythmias in different neuromuscular disorders and emphasizes the importance of managing arrhythmic cardiac manifestations.
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
Multidisciplinary Sciences
Jenny Setchell, Donya Mosleh, Laura McAdam, Patricia Thille, Thomas Abrams, Hugh J. McMillan, Bhavnita Mistry, Barbara E. Gibson
Summary: This paper evaluates a study that aimed to enhance clinical care for patients with muscular dystrophy and their families through regular dialogues with clinicians. The study found that the intervention led to changes in the clinical teams' thinking and practices regarding the emotional, social, and experiential aspects of living with the disease. However, there were differences between clinicians and clinics in the extent of these changes.
Article
Respiratory System
Sherri L. Katz, Jean K. Mah, Hugh J. McMillan, Craig Campbell, Vid Bijelic, Nick Barrowman, Franco Momoli, Henrietta Blinder, Shawn D. Aaron, Laura C. McAdam, The Thanh Diem Nguyen, Mark Tarnopolsky, David F. Wensley, David Zielinski, Louise Rose, Nicole Sheers, David J. Berlowitz, Lisa Wolfe, Doug McKim
Summary: This randomized controlled trial aimed to determine whether twice-daily lung volume recruitment (LVR) therapy attenuates the decline in forced vital capacity (FVC) at 2 years in boys with Duchenne muscular dystrophy (DMD). The results showed that there was no difference in decline in FVC with the use of twice-daily LVR for boys with relatively normal lung function.
Article
Biochemistry & Molecular Biology
Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Melissa Wigderson, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek
Summary: Onasemnogene abeparvovec was effective and well tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.
Article
Biochemistry & Molecular Biology
Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek
Summary: SPR1NT (NCT03505099) is a Phase III study investigating the efficacy and safety of onasemnogene abeparvovec in presymptomatic children with biallelic SMN1 mutations. The results showed that all 14 infants enrolled in the study were able to sit independently for at least 30 seconds within 18 months and none required permanent ventilation. The treatment was well tolerated and effective for children expected to develop SMA type 1.
Meeting Abstract
Endocrinology & Metabolism
Stefan Jackowski, Utkarsh Dang, Jinhui Ma, Maya Scharke, Victor Konji, Jacob Jaremko, Khaldoun Koujok, Mary-Ann Matzinger, Nazih Shenouda, Scott Walker, Colleen Hartigan, Lynn MacLeay, Nasrin Khan, Elizabeth Sykes, Hugh McMillan, Kerry Siminoski, Pradeep Bista, Maria Mancini, Joanne Donovan, Leanne Ward
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Meeting Abstract
Endocrinology & Metabolism
Stefan Jackowski, Utkarsh Dang, Maya Scharke, Victor Konji, Jacob Jaremko, Khaldoun Koujok, Mary-Ann Matzinger, Nazih Shenouda, Nasrin Khan, Lynn MacLeay, Elizabeth Sykes, Hugh McMillan, Kerry Siminoski, Paula Clemens, Michela Guglieri, Jean Mah, Eric Hoffman, Leanne Ward
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Irit Hochberg, Leigh A. M. Demain, Julie Richer, Kyle Thompson, Waheeda Pagarkar, Agusti Rodriguez-Palmero Seuma, Edgard Verdura, Aurora Pujol, Albert Amberger, Andrea J. Deutschmann, Sandra Demetz, James O'Sullivan, Meredith Gillespie, Inna A. Belyantseva, Hugh J. McMillan, Melanie Barzik, Jill E. Urquhart, Alessandro Rea, Glenda M. Beaman, Simon G. Williams, Sanjeev S. Bhaskar, Isabella R. Lawrence, Emma M. Jenkinson, Jessica L. Zambonin, Zeev Blumenfeld, Sergey Yalonetsky, Stephanie Oerum, Walter Rossmanith, Wyatt W. Yue, Johannes Zschocke, Kevin J. Munro, Brendan J. Battersby, Thomas B. Friedman, Robert W. Taylor, Raymond T. O'Keefe, William G. Newman
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Clinical Neurology
Kevin Strauss, Francesco Muntoni, Michelle Farrar, Kayoko Saito, Jerry Mendell, Laurent Servais, Hugh McMillan, Kathryn Swoboda, Jennifer Kwon, Craig Zaidman, Claudia Chiriboga, Susan Iannaccone, Jena Krueger, Julie Parsons, Perry Shieh, Sarah Kavanagh, Deepa Chand, Sitra Tauscher-Wisniewski, Thomas Macek
Meeting Abstract
Clinical Neurology
Maryam Oskoui, Victoria Hodgkinson, Bernard Brais, Craig Campbell, Joshua Lounsberry, Alex MacKenzie, Hugh McMillan, Jiri Vajsar, Lawrence Korngut