Phase 1/2 Study of Clenbuterol for the Treatment of Pompe Disease

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Pompe disease (Glycogen storage disease type II; acid maltase deficiency; MIM 232300) is a myopathy, similar to limb-girdle muscular dystrophy in its late-onset form, which results from acid a-glucosidase (GAA) deficiency in striated and smooth muscle. Enzyme replacement therapy (ERT) with recombinant human (rh) GAA has largely resulted in stabilization of the disease process from a pulmonary and motor perspective in late-onset Pompe disease. Lysosomal storage disorders such as Pompe disease can be more effectively treated, if the hurdle of cation-independent mannose-6-phosphate receptor (CI-MPR) uptake can be cleared. The paucity of CI-MPR in adult mammals' muscle has underscored the concept that CI-MPR is limiting for ERT in Pompe disease. Previously, low levels of CI-MPR were demonstrated in skeletal muscle of GAAKO mice, specifically in muscles comprised primarily of type II myofibers. Our preliminary results revealed that b2-agonist therapy enhanced CI-MPR expression and increased efficacy from GAA replacement therapy, thereby confirming the key role of CI-MPR with regard to replacement therapy in Pompe disease. Currently we plan a pilot clinical trial of b2-agonist therapy in patients with late-onset Pompe disease on ERT. The initial evaluation will include muscle strength testing, the 6 minute walk test, and pulmonary function testing. Evaluation of safety will include standard blood testing and electrocardiograms, while on study drug. Patients will continue on standard of care ERT throughout the trial. The study will be conducted at Duke University Hospital System with the review of the Duke Institutional Review Board under an investigator initiated IND.