Article
Neurosciences
David D. Fuller, Jorge A. Trejo-Lopez, Anthony T. Yachnis, Michael D. Sunshine, Sabhya Rana, Victoria E. Bindi, Barry J. Byrne, Barbara K. Smith
Summary: Pompe disease is a neuromuscular disorder caused by a gene mutation, with late-onset patients experiencing respiratory failure as a major cause of fatality. A case study of a late-onset PD patient revealed asynchronous bursting between diaphragms and motoneuron atrophy in the medulla and spinal cord. Histological assessment showed neuromuscular degeneration, indicating the need for therapy targeting the central nervous system alongside skeletal and cardiac muscle.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Genetics & Heredity
Laurike Harlaar, Pierluigi Ciet, Gijs van Tulder, Alice Pittaro, Harmke A. van Kooten, Nadine A. M. E. van der Beek, Esther Brusse, Piotr A. Wielopolski, Marleen de Bruijne, Ans T. van der Ploeg, Harm A. W. M. Tiddens, Pieter A. van Doorn
Summary: This study aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. Results showed that even in early-stage Pompe disease, the motion of the diaphragm is reduced and the shape is more curved during inspiration. MRI can be used to detect early signs of diaphragmatic weakness in Pompe patients, which might help to select patients for early intervention.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Multidisciplinary Sciences
Shih-hsin Kan, Jeffrey Y. Huang, Jerry Harb, Allisandra Rha, Nancy D. Dalton, Chloe Christensen, Yunghang Chan, Jeremy Davis-Turak, Jonathan Neumann, Raymond Y. Wang
Summary: This study generated a Gaa(em1935C>A) knock-in mouse model and a myoblast cell line carrying the Gaa c.1935C>A mutation using CRISPR-Cas9 technology. The homozygous Gaa(em1935C>A) mice recapitulated multiple characteristics of infantile-onset Pompe disease, making it an ideal model for evaluating innovative therapies for this disease.
SCIENTIFIC REPORTS
(2022)
Review
Medicine, General & Internal
Michele Umbrello, Edoardo Antonucci, Stefano Muttini
Summary: Maintaining spontaneous breathing in patients with acute respiratory failure can have both positive and negative effects on the lungs and diaphragm. Neurally adjusted ventilatory assist (NAVA) is an assist mode that provides proportional pressure to the respiratory system based on diaphragm activity. This ventilation mode has the potential to protect the lungs and respiratory muscles, reduce diaphragm disuse atrophy, and maintain patient-ventilator synchrony. This review summarizes the principles of NAVA technology, methods for setting the assist level, and findings from studies focused on lung and diaphragm protection, machine-patient interaction, and preservation of breathing pattern variability. The review also discusses the findings of clinical trials investigating the use of NAVA in acute respiratory failure.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
David Reyes-Leiva, Jorge Alonso-Perez, Mercedes Mayos, Claudia Nunez-Peralta, Jaume Llauger, Izaskun Belmonte, Irene Pedrosa-Hernandez, Sonia Segovia, Jordi Diaz-Manera
Summary: The study investigated the correlation between fat replacement in respiratory-related muscles and results of respiratory muscle function tests in late-onset Pompe disease patients, finding a positive relationship between fat replacement degree and worsening of lung function tests. This suggests the need for closer monitoring of patients with higher fat replacement levels in these muscle groups.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Leah B. Helou, Richard P. Dum
Summary: The diaphragm muscle plays a crucial role in various bodily functions. The research reveals that the primary motor cortex of monkeys has two separate sites representing the diaphragm, with no known connections between them. One site overlaps with trunk and axial musculature, while the other site overlaps with the origin of motor projections to a laryngeal muscle. This finding offers a new perspective for understanding functional imaging studies related to respiration and vocalization.
JOURNAL OF COMPARATIVE NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Naresh K. Meena, Davide Randazzo, Nina Raben, Rosa Puertollano
Summary: Gene therapy has shown potential in treating lysosomal storage disorders, such as Pompe disease, by reversing glycogen storage and improving cellular abnormalities. In a study, adeno-associated virus-mediated gene transfer successfully reversed glycogen storage in various target tissues and improved secondary cellular abnormalities in skeletal muscle. These findings lay the foundation for future clinical development in treating Pompe disease.
Article
Clinical Neurology
Jordi Diaz-Manera, Priya S. Kishnani, Hani Kushlaf, Shafeeq Ladha, Tahseen Mozaffar, Volker Straub, Antonio Toscano, Ans T. Van der Ploeg, Kenneth I. Berger, Paula R. Clemens, Yin-Hsiu Chien, John W. Day, Sergey Illarioshkin, Mark Roberts, Shahram Attarian, Joao Lindolfo Borges, Francoise Bouhour, Young Chul Choi, Sevim Erdem-Ozdamar, Ozlem Goker-Alpan, Anna Kostera-Pruszczyk, Kristina An Haack, Christopher Hug, Olivier Huynh-Ba, Judith Johnson, Nathan Thibault, Tianyue Zhou, Mazen M. Dimachkie, Benedikt Schoser
Summary: In this study, treatment with avalglucosidase alfa showed clinically meaningful improvement in respiratory function, ambulation, and functional endurance compared to alglucosidase alfa, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa.
Article
Clinical Neurology
Priya S. Kishnani, Jordi Diaz-Manera, Antonio Toscano, Paula R. Clemens, Shafeeq Ladha, Kenneth I. Berger, Hani Kushlaf, Volker Straub, Gerson Carvalho, Tahseen Mozaffar, Mark Roberts, Shahram Attarian, Yin-Hsiu Chien, Young-Chul Choi, John W. Day, Sevim Erdem-Ozdamar, Sergey Illarioshkin, Ozlem Goker-Alpan, Anna Kostera-Pruszczyk, Ans T. van der Ploeg, Kristina An Haack, Olivier Huynh-Ba, Swathi Tammireddy, Nathan Thibault, Tianyue Zhou, Mazen M. Dimachkie, Benedikt Schoser
Summary: In the COMET trial extension, avalglucosidase alfa treatment demonstrated clinically meaningful improvements in forced vital capacity and 6-minute walk test compared to alglucosidase alfa. The study showed that patients continuing avalglucosidase alfa treatment maintained positive clinical outcomes, while patients switching to avalglucosidase alfa had less improvement. No new safety concerns were observed.
Article
Multidisciplinary Sciences
Natalia Neumann-Klimasinska, T. Allen Merritt, Jennifer Beck, Izabela Miechowicz, Marta Szymankiewicz-Breborowicz, Tomasz Szczapa
Summary: The study demonstrated the feasibility and potential efficacy of heliox NIV-NAVA ventilation in preterm infants, showing a significant decrease in respiratory effort without affecting other monitored parameters. This therapy could enhance non-invasive respiratory support and reduce the risk of ventilatory failure in premature neonates.
SCIENTIFIC REPORTS
(2021)
Article
Pediatrics
Julie Lefevere, Brenda Van Delft, Michel Vervoort, Wilfried Cools, Filip Cools
Summary: The study examined the effect of changing NAVA levels during NIV-NAVA on electrical diaphragm activity in preterm infants with RDS. Preterm neonates displayed a biphasic response to changing NAVA levels with an identifiable breakpoint, suggesting careful monitoring is required due to immature neural feedback mechanisms.
EUROPEAN JOURNAL OF PEDIATRICS
(2022)
Article
Medicine, Research & Experimental
Peng Zou
Summary: This study compared the performance of two allometric scaling approaches and a body-weight-based dose conversion approach for dose prediction in gene therapy. The body-weight-based approach underestimated the dose in some vectors, while the allometric scaling approach overestimated the dose. The allometric scaling between log GEF and W-0.25 was appropriate in certain conditions.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biotechnology & Applied Microbiology
Sang-Oh Han, Dorothy Gheorghiu, Songtao Li, Hye Ri Kang, Dwight Koeberl
Summary: Pompe disease is a genetic disorder that can be corrected through gene therapy, but substantial transduction of liver cells is required. Research has found that a dose of 2 x 10(11) vg/kg can transduce all hepatocytes and achieve partial correction.
HUMAN GENE THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Sang-oh Han, Dorothy Gheorghiu, Alex Chang, Sweet Hope Mapatano, Songtao Li, Elizabeth Brooks, Dwight Koeberl
Summary: This study found that adding testosterone during gene therapy can significantly improve neuromuscular function, muscle strength, and biochemical indicators in female mice with Pompe disease, while oxandrolone has a certain improvement effect on biochemical indicators. These data confirm the benefits of brief androgen hormone treatment during gene therapy in mice with Pompe disease.
HUMAN GENE THERAPY
(2022)
Article
Medicine, General & Internal
E. E. Walsh, G. Perez Marc, A. M. Zareba, A. R. Falsey, Q. Jiang, M. Patton, F. P. Polack, C. Llapur, P. A. Doreski, K. Ilangovan, M. Ramet, Y. Fukushima, N. Hussen, L. J. Bont, J. Cardona, E. DeHaan, G. Castillo Villa, M. Ingilizova, D. Eiras, T. Mikati, R. N. Shah, K. Schneider, D. Cooper, K. Koury, M. -M Lino, A. S. Anderson, K. U. Jansen, K. A. Swanson, A. Gurtman, W. C. Gruber, B. Schmoele-Thoma
Summary: The RSVpreF vaccine showed efficacy in preventing RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness in adults (>= 60 years of age), with no evident safety concerns.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Biographical-Item
Biotechnology & Applied Microbiology
Barry J. Byrne, Angela L. McCall, Beverly L. Davidson, R. Jude Samulski
HUMAN GENE THERAPY
(2021)
Article
Genetics & Heredity
Sonja Neuser, Barbara Brechmann, Gali Heimer, Ines Broesse, Susanna Schubert, Lauren O'Grady, Michael Zech, Siddharth Srivastava, David A. Sweetser, Yasemin Dincer, Volker Mall, Juliane Winkelmann, Christian Behrends, Basil T. Darras, Robert J. Graham, Parul Jayakar, Barry Byrne, Bat El Bar-Aluma, Yael Haberman, Amir Szeinberg, Hesham M. Aldhalaan, Mais Hashem, Amal Al Tenaiji, Omar Ismayl, Asma E. Al Nuaimi, Karima Maher, Shahnaz Ibrahim, Fatima Khan, Henry Houlden, Vijayalakshmi S. Ramakumaran, Alistair T. Pagnamenta, Jennifer E. Posey, James R. Lupski, Wen-Hann Tan, Gehad ElGhazali, Isabella Herman, Tatiana Munoz, Gabriela M. Repetto, Angelika Seitz, Mandy Krumbiegel, Maria Cecilia Poli, Usha Kini, Stephanie Efthymiou, Jens Meiler, Reza Maroofian, Fowzan S. Alkuraya, Rami Abou Jamra, Bernt Popp, Bruria Ben-Zeev, Darius Ebrahimi-Fakhari
Summary: Bi-allelic TECPR2 variants are associated with a syndrome combining features of neurodevelopmental and neurodegenerative disorders, characterized by developmental delay, muscular hypotonia, and ataxia. Despite challenges in variant interpretation and pathogenicity classification, recommendations for reporting, assessment, and surveillance/treatment have been provided based on clinical, neuroimaging, and genetic data.
Article
Genetics & Heredity
Manuel A. Viamonte, Stephanie L. Filipp, Zara Zaidi, Matthew J. Gurka, Barry J. Byrne, Peter B. Kang
Summary: Research on Pompe disease has shown that different types of GAA gene variants are significantly associated with disease subtype, cardiomyopathy, age at diagnosis, and gross motor function. Multiple types of splice site variants beyond the classic one are often linked to milder phenotypes. Enzyme activity levels remain useful for supporting diagnosis when genetic variants are unclear.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Cardiac & Cardiovascular Systems
Barry J. Byrne, Steven D. Colan, Priya S. Kishnani, Meredith C. Foster, Susan E. Sparks, James B. Gibson, Kristina An Haack, David W. Stockton, Loren D. M. Pena, Si Houn Hahn, Judith Johnson, Pranoot X. Tanpaiboon, Nancy D. Leslie, David Kronn, Richard E. Hillman, Raymond Y. Wang
Summary: Pompe disease, caused by lysosomal acid alpha-glucosidase deficiency, leads to cardiomyopathy. Cardiac assessment is crucial for diagnosis and management. Results from the ADVANCE study show improvement in cardiac issues in Pompe disease patients after treatment with alglucosidase alpha.
CARDIOLOGY IN THE YOUNG
(2022)
Article
Neurosciences
David D. Fuller, Jorge A. Trejo-Lopez, Anthony T. Yachnis, Michael D. Sunshine, Sabhya Rana, Victoria E. Bindi, Barry J. Byrne, Barbara K. Smith
Summary: Pompe disease is a neuromuscular disorder caused by a gene mutation, with late-onset patients experiencing respiratory failure as a major cause of fatality. A case study of a late-onset PD patient revealed asynchronous bursting between diaphragms and motoneuron atrophy in the medulla and spinal cord. Histological assessment showed neuromuscular degeneration, indicating the need for therapy targeting the central nervous system alongside skeletal and cardiac muscle.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Editorial Material
Biotechnology & Applied Microbiology
Wuh-Liang Hwu, Shin-ichi Muramatsu, Yin-Hsiu Chien, Barry J. Byrne
Article
Biotechnology & Applied Microbiology
Chun-Hwei Tai, Ni-Chung Lee, Yin-Hsiu Chien, Barry J. Byrne, Shin-Ichi Muramatsu, Sheng-Hong Tseng, Wuh-Liang Hwu
Summary: Gene therapy with eladocagene exuparvovec in patients with aromatic L-amino acid decarboxylase deficiency leads to sustained and meaningful benefits, including improvements in motor and cognitive function, increased dopamine production, symptom relief, improved growth, and enhanced quality of life for patients and caregivers.
Article
Cardiac & Cardiovascular Systems
Shahryar Chowdhury, Lanier Jackson, Barry J. Byrne, Randall M. Bryant, W. Todd Cade, Tammy Lane Churchill, Julia Buchanan, Carolyn Taylor
Summary: Barth Syndrome is a mitochondrial cardioskeletal myopathy caused by gene defects, resulting in cardiomyopathy, muscle weakness, and exercise intolerance. This study identified cardiac risk factors that predict outcomes in Barth Syndrome, such as cardiac size, function, and QTc interval. Patients with worse cardiac manifestations and multiple risk factors are more likely to experience cardiac death or transplant. Close monitoring and intense therapy are needed for patients with progressive LV enlargement, dysfunction, and multiple cardiac risk factors.
PEDIATRIC CARDIOLOGY
(2022)
Article
Medicine, Research & Experimental
Prasad D. Trivedi, Chenghui Yu, Payel Chaudhuri, Evan J. Johnson, Tina Caton, Laura Adamson, Barry J. Byrne, Nicole K. Paulk, Nathalie Clement
Summary: The study optimized and compared the production of rAAV in suspension HEK293 cells by PEI-mediated transfection and HSV infection. The HSV production system yielded higher rAAV titers and full capsid percentages, but contained detectable levels of HSV DNA. The potency of rAAV stocks produced by both methods was found to be identical.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Cardiac & Cardiovascular Systems
Abhinandan Batra, Alison M. Barnard, Donovan J. Lott, Rebecca J. Willcocks, Sean C. Forbes, Saptarshi Chakraborty, Michael J. Daniels, Jannik Arbogast, William Triplett, Erik K. Henricson, Jonathan G. Dayan, Carsten Schmalfuss, Lee Sweeney, Barry J. Byrne, Craig M. McDonald, Krista Vandenborne, Glenn A. Walter
Summary: This study aimed to determine the rate of progressive decline in left ventricular function in DMD patients and identify early biomarkers of cardiac dysfunction. The findings revealed that DMD patients had worse left ventricular strain and it progressively declined over time. The use of cardioprotective drugs showed a positive impact on cardiac measures.
BMC CARDIOVASCULAR DISORDERS
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Barry J. Byrne, Melissa Elder, Carmen Leon-Astudillo, Manuela Corti
Letter
Orthopedics
Barbara K. Smith, Manuela Corti
Article
Biochemistry & Molecular Biology
Robert T. Mankowski, Stephanie E. Wohlgemuth, Guilherme Bresciani, A. Daniel Martin, George Arnaoutakis, Tomas Martin, Eric Jeng, Leonardo Ferreira, Tiago Machuca, Mindaugas Rackauskas, Ashley J. Smuder, Thomas Beaver, Christiaan Leeuwenburgh, Barbara K. Smith
Summary: Mechanical ventilation during cardiothoracic surgery can lead to ventilator-induced diaphragm dysfunction (VIDD) and delay recovery. In this study, intraoperative phrenic nerve stimulation was performed to offset VIDD and investigate changes in mitochondrial function.
Review
Biochemistry & Molecular Biology
Kia H. Markussen, Manuela Corti, Barry J. Byrne, Craig W. Vander Kooi, Ramon C. Sun, Matthew S. Gentry
Summary: This review discusses the primary role of glycogen in carbohydrate storage and energy metabolism in the liver and muscle, as well as its critical metabolic and non-metabolic roles in the brain. Perturbed glycogen functions are observed in various brain disorders, including neurological glycogen storage diseases. The study of glycogen and its treatment strategies is of great significance for human diseases.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Respiratory System
Priscila Sales de Campos, Wendy L. Olsen, James P. Wymer, Barbara K. Smith
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron death. Respiratory motor neuron impairments lead to various respiratory complications, ultimately accounting for a significant portion of morbidity and mortality in ALS. This review discusses respiratory therapies for ALS, including lung volume recruitment, mechanical insufflation-exsufflation, non-invasive ventilation, and respiratory strength training. It also introduces therapeutic acute intermittent hypoxia as a potential treatment to induce respiratory plasticity. The focus on emerging evidence and future work aims to improve survival for ALS patients.
CHRONIC RESPIRATORY DISEASE
(2023)