Therapeutic thoroughfares for adults living with Pompe disease

Abstract

Purpose of reviewPompe disease is caused by autosomal recessive mutations in the acid a-glucosidase gene leading to a multiorgan deficiency of the enzyme acid glucosidase alfa. To recover to a nondiseased status, a lift over a threshold of 25% acid glucosidase alfa enzyme activity is required. This update on therapeutic thoroughfares for adult Pompe disease aims to assist neuromuscular and metabolic specialists. Recent findingsWe reviewed the recent studies covering enzyme replacement therapy, gene therapy, and substrate reduction therapy in adult Pompe disease. Results of phase 3 studies and the first sets of long-term data of both novel enzyme replacement therapies, avalglucosidase alfa, and ciplaglucodsidase alfa combined with miglustat, are public. First gene therapy trials are ongoing. Substrate reduction therapy is in early transition to the clinical trial phase. We still miss dose escalation and intensification of frequency trials on enzyme replacement therapy in adults, probably suitable to echo current results in infantile and juvenile Pompe disease.

Current avenues of gene therapy in Pompe disease

“…A functional gene is introduced to substitute for the mutated gene, enabling endogenous production of GAA, which then undergoes natural posttranslational modifications for efficient trafficking to the lysosome [24]. It is crucial to target the right cells by selecting an appropriate vector capsid serotype, promoter, and route of administration [25].…”

Start, switch and stop (triple‐S) criteria for enzyme replacement therapy of late‐onset Pompe disease: European Pompe Consortium recommendation update 2024

“…Since then, two novel ERTs for late‐onset Pompe disease have been clinically evaluated in phase 3 trials and the first long‐term studies. Both novel ERTs reached marketing authorization by the European Medicines Agency and in several parts of the world in 2022 and 2023, respectively [ 4 , 5 , 6 , 7 , 8 ].…”