Review
Biochemistry & Molecular Biology
Marc Borie-Guichot, My Lan Tran, Yves Genisson, Stephanie Ballereau, Cecile Dehoux
Summary: Pompe disease is a lysosomal storage disease caused by mutations of the GAA gene, and the primary treatment is enzyme replacement therapy. Research on new therapies is ongoing due to limitations of ERT.
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)
Article
Pediatrics
Imke Anise Maartje Ditters, Hidde Harmen Huidekoper, Michelle Elisabeth Kruijshaar, Dimitris Rizopoulos, Andreas Hahn, Tiziana Enrico Mongini, Francois Labarthe, Marine Tardieu, Brigitte Chabrol, Anais Brassier, Rossella Parini, Giancarlo Parenti, Nadine Anna Maria Elisabeth van der Beek, Ans Tjitske van der Ploeg, Johanna Maria Pieternel van den Hout
Summary: This study assessed the effect of enzyme replacement therapy (ERT) with alglucosidase alfa on survival and walking ability in patients with classic infantile Pompe disease. The results showed that a high ERT dosage of 40 mg/kg per week significantly improved survival compared to the standard recommended dosage of 20 mg/kg every other week. These findings suggest a need for reconsideration of the currently registered dosage.
LANCET CHILD & ADOLESCENT HEALTH
(2022)
Article
Biochemistry & Molecular Biology
Valentina Sanchez-Porras, Johana Maria Guevara-Morales, Olga Yaneth Echeverri-Pena
Summary: Pompe disease is caused by mutations in the GAA gene, leading to the accumulation of lysosomal glycogen in muscular tissue. Autophagic buildup is a major factor affecting skeletal muscle, and understanding the interconnected mechanisms is important for addressing clinical differences in skeletal and cardiac involvement. This study presents a network reconstruction based on a literature review and database analysis, discussing the role of various intermediates in the pathologic cascade and their relationship with mTORC1/AMPK.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Alicia Dorneles Dornelles, Ana Paula Pedroso Junges, Tiago Veiga Pereira, Barbara Correa Krug, Candice Beatriz Treter Goncalves, Juan Clinton Llerena Jr, Priya Sunil Kishnani, Haliton Alves de Oliveira Jr, Ida Vanessa Doederlein Schwartz
Summary: This study reviewed the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset Pompe disease (LOPD). Results indicated improvements in walking ability, quality of life, and ventilation time with GAA ERT, while adverse events were mild.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biology
Jason Wang, Chris J. Zhou, Alastair Khodabukus, Sabrina Tran, Sang-Oh Han, Aaron L. Carlson, Lauran Madden, Priya S. Kishnani, Dwight D. Koeberl, Nenad Bursac
Summary: The study developed a 3D in vitro model of human skeletal muscle that recapitulates the pathophysiology of Pompe disease. They identified a Pompe disease-specific transcriptional signature and observed a partial reversal of the signature upon in vitro treatment of myobundles with rhGAA.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Medicinal
Atsushi Kato, Izumi Nakagome, Uta Kanekiyo, Tian-Tian Lu, Yi-Xian Li, Kosuke Yoshimura, Mana Kishida, Kenta Shinzawa, Tomoki Yoshida, Nobutada Tanaka, Yue-Mei Jia, Robert J. Nash, George W. J. Fleet, Chu-Yi Yu
Summary: In recent years, pharmacological chaperones have been recognized as thermodynamic stabilizers in combination therapy. This study focused on designing a high-affinity ligand for lysosomal acid alpha-glucosidase (GAA) using alkyl branches on 1-deoxynojirimycin (DNJ). The results showed that 5-C-heptyl-DNJ significantly improved the stability of recombinant human acid alpha-glucosidase (rhGAA) and increased intracellular GAA activities in cells from Pompe disease patients.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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
Biochemistry & Molecular Biology
Konstantin O. Muranov, Nicolay B. Poliansky, Vera A. Borzova, Sergey Y. Kleimenov
Summary: aH-Crystallin, a high molecular weight form of α-crystallin, plays a significant role in the development of cataracts. Refolding with urea increases the chaperone-like activity of α-crystallin and HMWA, while reducing their sizes. The chaperone-like activity of a-crystallin and HMWA correlates with denaturation enthalpy, suggesting a correction of misfolded proteins and rearrangement of protein structures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Roberta Iacono, Nadia Minopoli, Maria Carmina Ferrara, Antonietta Tarallo, Carla Damiano, Caterina Porto, Sandra Strollo, Veronique Roig-Zamboni, Gianfranco Peluso, Gerlind Sulzenbacher, Beatrice Cobucci-Ponzano, Giancarlo Parenti, Marco Moracci
Summary: Pompe disease is a genetic metabolic disorder caused by a deficiency of lysosomal acid alpha-glucosidase (GAA). The approved treatment is enzyme replacement therapy with rhGAA. Recent discovery of novel chaperones such as L- and D-carnitine and acetyl-D-carnitine has shown promising synergistic effects with rhGAA in enhancing enzyme activity in Pompe patients' fibroblasts.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Medicine, General & Internal
Vincenza Gragnaniello, Caterina Rizzardi, Anna Commone, Daniela Gueraldi, Evelina Maines, Leonardo Salviati, Giovanni Di Salvo, Alberto B. Burlina
Summary: For the first time, this report describes a case of infantile Pompe disease in which hypertrophic cardiomyopathy evolved into non-compaction myocardium after treatment. The patient was initially treated with standard enzyme replacement therapy and immunomodulation cycles, but the hypertrophic cardiomyopathy did not resolve. After switching to a new combination therapy, the cardiac hypertrophy resolved but transformed into non-compaction myocardium.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cell Biology
Paul Dent, Laurence Booth, Jane L. Roberts, Andrew Poklepovic, Derek Cridebring, Eric M. Reiman
Summary: Aberrant expression and denaturation of Tau, amyloid-beta and TDP-43 can lead to cell death and is a major component of pathologies such as Alzheimer's Disease. Drugs like AR12 and Neratinib show potential in reducing the levels of these proteins through modulation of ATPase activity and macroautophagy. The study also highlights the importance of autophagy in protein degradation and potential treatments for AD.
Article
Immunology
Anne S. De Groot, Ankit K. Desai, Sandra Lelias, S. M. Shahjahan Miah, Frances E. Terry, Sundos Khan, Cindy Li, John S. Yi, Matt Ardito, William D. Martin, Priya S. Kishnani
Summary: PIMA study aims to develop a tool to quantify T cell epitopes for predicting the risk of developing anti-drug antibodies in infantile-onset Pompe disease children. The tool combines EpiMatrix and HLA-restricted iTEM, and can be used to assess ADA risk. The study confirmed the immunomodulatory effect of GAA epitopes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Qiushi Liang, Joon M. Pijnenburg, Erikjan Rijkers, Arnold G. Vulto, Ans T. van der Ploeg, Niek P. van Til, Eva C. Vlaar, Jeroen A. A. Demmers, W. W. M. Pim Pijnappel
Summary: Pompe disease is a lysosomal storage disorder characterized by glycogen accumulation in skeletal muscle, leading to profound pathology. This study showed that lentiviral gene therapy with LV-IGF2.GAAco can nearly completely correct disease-associated proteomic changes, supporting its future clinical development as a new treatment option for Pompe disease.
JOURNAL OF PROTEOMICS
(2024)
Article
Pediatrics
Rodrigo Tzovenos Starosta, Ying-Chen Claire Hou, Katelyn Leestma, Prapti Singh, Luke Viehl, Linda Manwaring, Jorge Luis Granadillo, Molly C. Schroeder, Jamie N. Colombo, Halana Whitehead, Patricia Irene Dickson, Monica L. Hulbert, Hoanh Thi Nguyen
Summary: Infantile-onset Pompe disease (IOPD) and sickle cell anemia (SCA) are two rare diseases that can coexist. This report highlights the importance of early intervention and treatment for patients with this complex presentation.
FRONTIERS IN PEDIATRICS
(2022)
