Current avenues of gene therapy in Pompe disease

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.

Clinical Genetic and Genomic Testing in Congenital Heart Disease and Cardiomyopathy

“…Enzyme replacement therapy can be used for certain lysosomal storage disorders. For instance, a therapy has been available for patients with Fabry disease since 2001 and for those with Pompe disease since 2006 [87,88]. Ongoing investigations are being conducted for gene therapies, and autologous hematopoietic stem cell transplants of cells treated with lentiviral vectors [87,88].…”

“…For instance, a therapy has been available for patients with Fabry disease since 2001 and for those with Pompe disease since 2006 [87,88]. Ongoing investigations are being conducted for gene therapies, and autologous hematopoietic stem cell transplants of cells treated with lentiviral vectors [87,88]. In June 2023, the Food and Drug Administration approved a therapy for Duchenne muscular dystrophy (DMD) which has the potential to impact cardiomyopathies [89].…”