NEW YORK REGION THALASSEMIA CENTER

(改编自申请人的摘要)这项工作的总体目标 建议建立纽约地区地中海贫血中心(NYRTC)， 可以参与NIH地中海贫血的发展和建立 临床研究网络(TCRN)。地中海贫血和地中海贫血的关键研究 对新疗法的有意义的评估将大大增强 创建这个网络。在前期工作中，调查人员已经 发展了一个由12个地区机构组成的集团，涉及200多个 患者，并已开始汇编患者数据库。NYRTC成员 已经确定了两个主要的调查对象作为 合作试验：丙型肝炎病毒感染和骨质疏松症。第一 研究建议联合疗法治疗丙型肝炎，丙型肝炎是 患者在血液筛查前输血，这会增加患病风险 铁超载和丙型肝炎引起的肝病(纤维化、肝硬变、癌症)。 仅干扰素在10%的病例中有效。试点研究结合 干扰素和利巴韦林显示出希望。调查人员提议包括 分析患者铁状况和宿主特异性疾病修饰物，包括 HFE基因的突变。这些突变会影响胃肠道铁。 研究人员发现，吸收与低CD8有关 免疫型。第二项研究集中在评估和治疗上 骨质疏松。铁超载直接和间接影响骨代谢 间接通过对免疫、内分泌和造血系统的影响。 骨形成和骨吸收的标志物将与骨矿物质相关 密度和各种与铁有关的参数以及上述 提到了宿主特定的疾病修饰物。将进行临床试验 对帕米磷酸钠的有效性进行评估，帕米磷酸钠是一种抑制 骨吸收。同样，铁和疾病修饰物的影响将是 检查过了。这些研究非常适合多中心合作。

(Adapted from the applicant's abstract) The overall objective of this proposal is to establish a New York Regional Thalassemia Center (NYRTC) that could participate in the development and establishment of the NIH Thalassemia Clinical Research Network (TCRN). Key research in thalassemia and the meaningful evaluation of new therapies would be greatly enhanced by the creation of this network. In preliminary work, the investigators have developed a group of 12 regional institutions caring for more than 200 patients and have begun compiling a patient database. Members of the NYRTC have identified two central subjects for investigation as models for collaborative trials: hepatitis C( HCV) infection and osteoporosis. The first study proposes combination therapy to treat HCV, a complication common among patients transfused before blood screening which leads to increased risk of liver disease (fibrosis, cirrhosis, cancer) from both iron overload and HCV. Interferon alone is effective in only 10% of cases. Pilot studies combining interferon and ribavirin show promise. The investigators propose to include analysis of iron status patient and host specific disease modifiers, including mutations of the HFE gene. These mutations affect gastrointestinal iron absorption and the investigators have found are associated with low CD8 immunotype. The second study centers on evaluation and treatment of osteoporosis. Iron overload influences bone metabolism both directly and indirectly through effects on the immune, endocrine and hematopoietic systems. Markers of bone formation and resorption will be correlated with bone mineral density and a variety of iron-related parameters as well as the above mentioned host specific disease modifiers. A clinical trial will be undertaken to assess the effectiveness of pamidronate, a drug that inhibits bone resorption. Again, the impact of iron and the disease modifiers will be examined. These studies are ideally suited to multicenter collaborations.