Commentary
Video
Critical Lessons From Emergence of Enzyme Replacement Therapies in Pompe Disease: Priya Kishnani, MD
Author(s):
The professor of pediatrics and division chief of Medical Genetics at Duke University delved into the transformative impact of enzyme replacement therapy on Pompe disease, addressing its advancements, limitations, and promising innovations shaping its future. [WATCH TIME: 2 minutes]
WATCH TIME: 2 minutes
"At the crux of the matter is still understanding the disease, and I think newborn screening has allowed us that greatly."
Pompe disease is a rare genetic disorder caused by mutations in the GAA gene, leading to deficiency of acid alpha-glucosidase, an enzyme responsible for breaking down glycogen in lysosomes. The resulting glycogen accumulation primarily affects skeletal, cardiac, and respiratory muscles, causing progressive muscle weakness and, in severe cases, lift-threatening complications. Treatment has evolved significant since the introduction of enzyme replacement therapy (ERT) with algucosidase alfa, which transformed the prognosis for infantile-onset and late-onset Pompe disease.
Priya Kishnani, MD, a professor of pediatrics and division chief of Medical Genetics at Duke University, chaired a session at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific conference, held March 16-19 in Dallas, Texas, on the mechanisms, therapeutic advances, advocacy, and integrated care approaches to Pompe disease. In the track session, which featured clinical insights from 7 different clinicians, Kishnani focused on historical learnings from pre-ERT to the current ERT landscape in Pompe disease, as well as how the role of newborn screening has improved early intervention.
At the conference, Kishnani sat down with NeurologyLive® to discuss the evolution of ERT, highlighting its transformative impact and limitations. Kishnani, a clinical and biochemical geneticist by training, emphasized the critical importance of targeting skeletal muscle, advancements in next-generation therapies, and the need to address immunogenicity and mult-domain targeting. Furthermore, she also explored the future potential of substrate reduction chaperone therapy, and gene-based approaches while stressing the pivotal function of newborn screening in improving early diagnosis and outcomes.
