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CRIM Responses in Pompe Disease

CRIM 对庞贝病的反应

基本信息

批准号：
8381320
负责人：
Piya S Kishnani
金额：
$ 7.19万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8381320
关键词：
Acids Age Alpha-glucosidase Antibodies Biological Assay Cardiology Cardiomyopathies Caring Cause of Death Clinical Clinical Protocols Clinical Research Clinical Trials Network Collaborations Control Groups Cost Sharing DNA Data Data Analyses Data Base Management Data Set Disease Disease Outcome Enrollment Failure Fibroblasts Future Genomics Genotype Glycogen Storage Disease Glycogen storage disease type II Grant Human Immune Immune Tolerance Immune response Immunology Immunosuppression International Laboratories Laboratory Diagnosis Lung Minority Monitor Natural History Outcome Patients Phenotype Physical therapy Protocols documentation Recombinants Recording of previous events Regimen Research Design Research Institute Research Personnel Residual state Resources Series Skin Therapeutic Therapeutic immunosuppression Western Blotting age group base design enzyme replacement therapy enzyme therapy improved infancy infant death novel therapeutic intervention pediatric department prospective response skills statistics

项目摘要

Pompe disease (Glycogen storage disease type II; MIM 232300) is a classical lysosomal storage disorder that causes death in the first year of life for patients with the infantile form due to a progressive cardiomyopathy leading to cardiorespiratory failure. Myozyme (alglucosidase alpha, recombinant human acid alpha-glucosidase/GAA, rhGAA) was approved in April 2006 as a treatment for Pompe Disease. The availability of ERT with Myozyme has improved the outcome of most patients with Pompe disease; however, a subset of infantile Pompe patients responds poorly to ERT, subsequently dying from cardiorespiratory failure. Poorly-responding Pompe disease patients generally lack residual GAA expression and these patients are cross-reacting immune material-negative (CRIM-negative). The Aims of this proposal would evaluate these rare CRIM-negative Pompe disease patients on ERT +/- immune suppression, by enrolling them in a prospective/retrospective natural history study through the Lysosomal Disease Network. Subjects would be enrolled from the Network and data collected regarding a number of clinical endpoints to determine the natural history of this disorder. Enrollment will include patients for whom a poor clinical response to current therapy is predicted. Patients studied will be all infantile crossreacting immune material (CRIM)-negative Pompe disease patients on a clinical protocol starting enzyme replacement therapy (ERT) with or without immune suppression. They will be compared to data obtained from infantile CRIM-positive Pompe disease patients started on ERT at similar ages and also enrolled in the protocol monitoring history and outcome of the disease on ERT.

庞贝病（糖原贮积病 II 型；MIM 232300）是一种经典的溶酶体贮积病由于进行性进展，导致婴儿型患者在生命的第一年死亡心肌病导致心肺衰竭。 Myozyme（α葡萄糖苷酶，重组人酸性α-葡萄糖苷酶/GAA，rhGAA）于2006年4月被批准用于庞贝病的治疗。这使用 Myozyme 进行 ERT 改善了大多数庞贝病患者的预后；然而，一部分婴儿庞贝氏症患者对 ERT 反应不佳，随后死于心肺疾病失败。反应不佳的庞贝病患者通常缺乏残留的 GAA 表达，这些患者的交叉反应免疫物质呈阴性（CRIM 阴性）。该提案的目的是评估这些罕见的 CRIM 阴性庞贝病患者的 ERT +/- 免疫抑制，通过将他们纳入前瞻性/回顾性自然历史研究溶酶体疾病网络。受试者将从网络中登记并收集有关确定这种疾病的自然史的临床终点数量。注册将包括患者预计对当前治疗的临床反应不佳。研究的患者都将出现婴儿交叉反应免疫物质（CRIM）阴性庞贝病患者接受临床方案启动酶有或没有免疫抑制的替代疗法（ERT）。他们将与获得的数据进行比较来自婴儿 CRIM 阳性庞贝病患者的患者在相似的年龄开始接受 ERT，并且还参加了方案监测 ERT 疾病史和结果。