GAA ACTIVITY AND GENE MUTATIONS IN PATIENTS WITH LATE ONSET POMPE DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Pompe病是一种罕见的常染色体隐性代谢性肌肉疾病，由酸α糖苷酶（GAA）缺乏引起，GAA是一种用于降解溶酶体糖原的关键酶。在庞贝病中，大量的糖原积聚在各种组织中，尤其是骨骼肌，从而阻碍了它们的正常功能。Genzyme公司生产了一种重组形式的人酸性α -葡萄糖苷酶（rhGAA）， Myozyme，一种用于庞贝病的研究性酶替代疗法（ERT）。希望ERT能恢复溶酶体GAA活性，消耗积累的溶酶体糖原，防止底物进一步积累。rhGaa是由中国仓鼠卵巢细胞产生的，其中编码GAA的互补脱氧核糖核酸（cDNA）已稳定表达。婴儿发病形式的临床试验目前已停止登记。目前，新诊断的婴儿发病患者可以在Genzyme发起的扩大准入计划下接受ERT。迟发性前瞻性观察研究（LOPOS）于2004年开始，纳入了58例轻度至中度迟发性庞贝病患者。临床试验必须开始为成人患者应对晚发性庞贝病。该方案将筛选参与这些临床试验的潜在患者。假设：该筛选方案旨在评估未来Myozyme临床试验的潜在候选人并确定合适的参与者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pompe disease is rare autosomal recessive metabolic muscle disease caused by a deficiency or lack of acid alpha glycosidase (GAA), a critical enzyme used to degrade lysosomal glycogen. In Pompe disease, an excessive amount of glycogen builds up in various tissues, especially skeletal muscle, that prevents their normal function. Genzyme Corporation has manufactured a recombinant form of human acid alpha-glucosidase, (rhGAA), Myozyme, an investigational enzyme replacement therapy (ERT) for Pompe disease. It is hoped that ERT will restore lysosomal GAA activity, deplete accumulated lysosomal glycogen, and prevent further substrate accumulation. rhGaa is produced from Chinese hamster ovary cells into which the complementary deoxyribonucleic acid (cDNA) coding for GAA has been stably expressed. Clinical trials for infantile onset form are currently closed to enrollment. Presently newly diagnosed infantile onset patients may receive ERT under an expanded access program initiated by Genzyme. The late-onset Prospective Observational Study (LOPOS) began in 2004 and is fully enrolled with 58 individuals with mild to intermediate late-onset Pompe Disease. Clinical trials must begin for adult patients coping with late-onset Pompe disease. This protocol will screen potential patients for participation in these clinical trials. Hypothesis: This screening protocol is designed to evaluate potential candidates for future Myozyme clinical trials and identify suitable participants.