CLINICAL TRIAL: PHASE II STUDY OF COMBINED LARONIDASE (ALDURAZYME) ENZYME REPLAC

临床试验：联合 Laronidase (ALDURAZYME) 酶 REPLAC 的 II 期研究

• 批准号: 7951663
• 负责人: PAUL J ORCHARD
• 金额: $ 0.84万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951663
• 关键词: 8 year old; Cessation of life; Child; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Deposition; Deterioration; Development; Dose; Enzymes; Excretory function; FDA approved; Funding; Glycosaminoglycans; Grant; Hematopoietic stem cells; Human; Inherited; Institution; L-Iduronidase; Lung; Mechanical ventilation; Metabolic Diseases; Mucopolysaccharidosis I H; Neurocognitive; Obstructive Sleep Apnea; Patients; Phase II Clinical Trials; Psyche structure; Recombinants; Research; Research Personnel; Resources; Risk; Source; Transplantation; United States National Institutes of Health; Ventilator; Visceral; airway obstruction; base; enzyme replacement therapy; high risk; improved; urinary

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. Hurler Syndrome (MPS-IH), an inherited metabolic disease is characterized by progressive mental decline and death by 5 to 8 years of age. Hematopoietic stem cell transplatation (HSCT) is the only proven therapy that can stabilize neurocognitive development and improve survival in patients with Hurler syndrome. However, children with Hurler syndrome are at high risk for transplant related complications, particularly pulmonary hemmorrhage and upper airway obstruction often leading to requirement for mechanical ventilation. Recombinant human alpha-L-iduronidase, laronidase (Aldurazyme) enzyme replacement therapy (ERT) is FDA-approved for MPS-I. Laronidase ERT, when administered on a weekly basis, decreases body load of abnormally accumulated glycosaminoglycans (GAG) and its symptomatology, such as upper airway obstruction (obstructive sleep apnea), visceral deposits (hepatospenomegaly) and urinary excretion of GAG in patients with MPS-I. However, ERT has not been shown to benefit the neurocognitive deterioration or improve survival; therefore, HSCT remains the mainstay of therapy for patients with Hurler syndrome. As ERT can decrease airway GAG deposits and obstructive sleep apnea in patients with MPS-I, we hypothesize that weekly laronidase (0.58 mg/kg/dose IV) ERT for 12 weeks prior to HSCT and 8 weeks following HSCT will result in a decreased GAG burden that is associated with improved 1-year overall survival and decreased risk of Hurler-related pulmonary complications following HSCT, such as ventilator therapy due to pulmonary hemmorrhage and airway obstruction.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 Hurler 综合征 (MPS-IH) 是一种遗传性代谢疾病，其特征是进行性智力衰退，并在 5 至 8 岁时死亡。造血干细胞移植（HSCT）是唯一经过验证的可以稳定神经认知发育并提高 Hurler 综合征患者生存率的疗法。 然而，患有 Hurler 综合征的儿童发生移植相关并发症的风险很高，特别是肺出血和上呼吸道阻塞，通常导致需要机械通气。 重组人 α-L-艾杜糖醛酸酶、laronidase (Aldurazyme) 酶替代疗法 (ERT) 已获得 FDA 批准用于 MPS-I。 每周给予 Laronidase ERT 可以减少 MPS-I 患者异常积累的糖胺聚糖 (GAG) 的身体负荷及其症状，例如上气道阻塞（阻塞性睡眠呼吸暂停）、内脏沉积（肝肾肿大）和 GAG 尿排泄。然而，ERT 尚未被证明可以改善神经认知恶化或提高生存率；因此，HSCT 仍然是 Hurler 综合征患者的主要治疗方法。 由于 ERT 可以减少 MPS-I 患者气道 GAG 沉积和阻塞性睡眠呼吸暂停，我们假设 HSCT 前 12 周和 HSCT 后 8 周每周进行拉罗尼酶（0.58 mg/kg/剂量 IV）ERT 将减少 GAG 负担，这与改善 1 年总生存率和降低 HSCT 后 Hurler 相关肺部并发症（如呼吸机）的风险有关 由于肺出血和气道阻塞而需要治疗。