Pompe disease is a fatal neuromuscular disorder resulting from mutations in the gene for acid alpha-glucosidase (GAA) – an enzyme necessary to degrade lysosomal glycogen. Infants with Pompe disease suffer from respiratory insufficiency often leading to mechanical ventilation.
The only FDA-approved therapy is enzyme replacement therapy (ERT) but this therapy does not cure the muscle and CNS problems that these children encounter. Children with this disease have a weak diaphragm and upper airway dysfunction and often need a tracheostomy tube. Despite ERT, they often become dependent on a ventilator for breathing because the muscles are not fully treated with ERT. In addition, because ERT does not cross the blood brain barrier, the CNS pathology is not targeted by ERT.
No treatment currently exists for both the CNS and muscular pathology of Pompe Disease. This research will help us better understand the mechanisms of CNS pathology involved in Pompe disease and the role of gene therapy in treating the CNS and muscular component of upper airway problems.
Gene therapy strategy for Pompe disease
Our lab focuses on the correction of the respiratory pathophysiology of Pompe disease using a Pompe disease mouse model (the Gaa-/-mouse). Using efferent nerve recordings, we are studying the impact of compounds that enhance excitatory glutaminergic neural transmission in respiratory neurons. Using rodent respiratory physiology outcome measures, such as whole-body plethysmography, forced oscillometry, and efferent nerve outputs we can study the impact of gene therapy on breathing.
