(No more than 30 lines) Pompe Disease is an inherited metabolic neuromyopathy caused by acid ?-glucosidase (GAA) deficiency/absence, which results in lysosomal glycogen accumulation and extensive tissue damage, especially in muscles. Alglucosidase alfa, an enzyme replacement therapy (ERT), has been approved for treating all patients with Pompe disease. Unfortunately, the patient population with Pompe disease is heterogeneous, with many patients not developing clear symptoms until the muscle pathology has advanced beyond glycogen accumulation, reducing the efficacy of ERT. There is a lack of means to map glycogen distribution in Pompe patients, characterize its progressive buildup and, more importantly, guide ERT treatment. The present project proposes to develop non-invasive and quantitative muscle glycogen MRI, addressing an unmet need in Pompe research. The central hypothesis is that optimized glycogen MRI enables non-invasive and quantitative imaging of muscle glycogen accumulation, a key feature of Pompe disease. Specifically, aim 1 will develop and improve the sensitivity of glycogen CEST imaging in tissue-mimicking glycogen-gel phantoms.
Aim 2 will validate glycogen MRI as an imaging biomarker of Pompe disease progression by longitudinally monitoring muscle glycogen accumulation in GAAKO mice before symptom onset. The goal is to establish muscle glycogen MRI as a unique imaging technique for Pompe disease and ultimately, may be applied to guide ERT treatment.
(No more than 2 ? 3 Sentences) Pompe disease is an inherited metabolic neuromyopathy caused by acid ?-glucosidase deficiency, causing massive lysosomal glycogen accumulation, especially in muscles. Although enzyme replacement therapy (ERT) has been approved for treating Pompe disease, the patient population is heterogeneous, with many patients not developing clear symptoms until the muscle pathology has advanced beyond glycogen accumulation, reducing the efficacy of ERT. The project aims to develop non-invasive glycogen MRI to monitor muscle glycogen buildup, addressing an unmet need in Pompe research.