AI Article Synopsis
- Pompe disease is a serious inherited disorder that results in muscle weakness and neurological issues due to glycogen buildup, and while enzyme replacement therapy has improved patient outcomes, it has limitations.
- Gene therapy is emerging as a promising alternative, especially for addressing neurological aspects of the disease, with recent studies focusing on the use of recombinant adeno-associated virus (rAAV) and lentiviral vectors (LV).
- Current research shows that gene therapy could potentially correct the core issues of Pompe disease, but there are still challenges to tackle, including vector production, immune responses, and the possibility of needing to redose patients.
Article Abstract
Purpose Of Review: Pompe disease is a rare, inherited, devastating condition that causes progressive weakness, cardiomyopathy and neuromotor disease due to the accumulation of glycogen in striated and smooth muscle, as well as neurons. While enzyme replacement therapy has dramatically changed the outcome of patients with the disease, this strategy has several limitations. Gene therapy in Pompe disease constitutes an attractive approach due to the multisystem aspects of the disease and need to address the central nervous system manifestations. This review highlights the recent work in this field, including methods, progress, shortcomings, and future directions.
Recent Findings: Recombinant adeno-associated virus (rAAV) and lentiviral vectors (LV) are well studied platforms for gene therapy in Pompe disease. These products can be further adapted for safe and efficient administration with concomitant immunosuppression, with the modification of specific receptors or codon optimization. rAAV has been studied in multiple clinical trials demonstrating safety and tolerability.
Summary: Gene therapy for the treatment of patients with Pompe disease is feasible and offers an opportunity to fully correct the principal pathology leading to cellular glycogen accumulation. Further work is needed to overcome the limitations related to vector production, immunologic reactions and redosing.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10911405 | PMC |
| http://dx.doi.org/10.1097/WCO.0000000000001187 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Highlights of Precision Medicine, Genetics, Epigenetics and Artificial Intelligence in Pompe Disease.
Int J Mol Sci
January 2025
Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy.
Pompe disease is a neuromuscular disorder caused by a deficiency of the enzyme acid alpha-glucosidase (), which leads to lysosomal glycogen accumulation and progressive development of muscle weakness. Two distinct isoforms have been identified. In the infantile form, the weakness is often severe and leads to motor difficulties from the first few months of life.
View Article and Find Full Text PDFGut-Heart Axis: Microbiome Involvement in Restrictive Cardiomyopathies.
Biomedicines
January 2025
Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, Instituto Nacional de Cardiología Ignacio Chávez, Universidad Nacional Autónoma de México, Mexico City 14080, Mexico.
An intriguing aspect of restrictive cardiomyopathies (RCM) is the microbiome role in the natural history of the disease. These cardiomyopathies are often difficult to diagnose and so result in significant morbidity and mortality. The human microbiome, composed of billions of microorganisms, influences various physiological and pathological processes, including cardiovascular health.
View Article and Find Full Text PDFClinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes.
Ital J Pediatr
January 2025
Pediatrics Department, Genetics Unit, Mansoura University, Mansoura, Egypt.
Background: Pompe disease is a rare genetic disorder caused by a deficiency of the enzyme acid alpha-glucosidase. This condition leads to muscle weakness, respiratory problems, and heart abnormalities in affected individuals.
Methods: The aim of the study is to share our experience through cross sectional study of patients with infantile-onset Pompe disease (IOPD) with different genetic variations, resulting in diverse clinical presentations.
Engineering of a lysosomal-targeted GAA enzyme.
Protein Eng Des Sel
January 2025
Pfizer Rare Disease Research Unit, 610 Main Street, Cambridge, MA 02139, United States.
Pompe disease is a tissue glycogen disorder caused by genetic insufficiency of the GAA enzyme. GAA enzyme replacement therapies for Pompe disease have been limited by poor lysosomal trafficking of the recombinant GAA molecule through the native mannose-6-phosphate-mediated pathway. Here, we describe the successful rational engineering of a chimeric GAA enzyme that utilizes the binding affinity of a modified IGF-II moiety to its native receptor to bypass the mannose-6-phosphate-mediated lysosomal trafficking pathway, conferring a significant increase in cellular uptake of the GAA enzyme.
View Article and Find Full Text PDFParent Reports of Developmental Service Utilization After Newborn Screening.
Int J Neonatal Screen
December 2024
RTI International, 3040 E. Cornwallis Road, Research Triangle Park, P.O. Box 12194, Research Triangle Park, NC 27709, USA.
Newborn screening (NBS) presents an opportunity to identify a subset of babies at birth who are at risk for developmental delays and could benefit from a range of developmental services. Potential developmental services in the United States include Part C Early Intervention (EI), private therapies, and school-based services. Using parent-reported outcomes, this study examined the rates at which a sample of children diagnosed with NBS conditions used each developmental service.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!