ORAL L GLUTAMINE THERAPY FOR SICKLE CELL ANEMIA

描述：镰状细胞性贫血是最常见和最具破坏性的疾病之一。 具有显著发病率和死亡率的遗传性疾病影响 有非裔美国人血统的人。目前还没有安全有效的治疗方法 可用。在过去的几年里，羟基脲已经被用于一种 镰状细胞性贫血患者数量不断增加。然而，羟基脲是一种 具有骨髓抑制作用的化疗药物及其长期应用 安全仍是个未知数。一个理想的药剂应该是一种容易 即使长期使用，也是可用、有效和安全的。基于之前的数据 从这个实验室对镰刀状的红细胞新陈代谢，我们进行了 最近进行了一项使用L-谷氨酰胺作为口服剂的试点研究。四个星期 涉及7名纯合子血红蛋白S患者的开放标记研究显示 通过展示氧化还原电位的改善和 所有患者的慢性疼痛均有所减轻。此外，接下来的12周 涉及4名患者的研究显示， 痛苦的镰刀危机。根据这些数据，我们建议扩大 L-谷氨酰胺治疗镰状细胞性贫血的双盲研究 客观观察氨基酸在镰状细胞性贫血中的作用 患者的临床状态和血液学参数。 我们的长期目标是确定L-谷氨酰胺的有效性和安全性 治疗镰状细胞性贫血。我们在这个项目中的具体目标是 测定口服L-谷氨酰胺对1)镰状红细胞的影响 细胞和生化水平，2)镰状细胞性贫血的临床状况 患者包括疼痛危象的发生率、麻醉药品需求量 急性或慢性疼痛，3)镰状细胞性贫血患者的血液学 包括血红蛋白、红细胞压积、网织红细胞计数和 己糖激酶水平；4)L-谷氨酰胺的不良反应。 L-谷氨酰胺是一种被广泛用于其他目的的氨基酸 并被其他人证明是安全的。它也很便宜，而且很容易 可用。试点数据令人振奋。该项目将提供 使用L-谷氨酰胺的病理生理基础，并将评估 L-谷氨酰胺治疗镰状细胞性贫血疗效观察

DESCRIPTION: Sickle cell anemia is one of the most common and devastating hereditary disorders with significant morbidity and mortality affecting individuals of African American heritage. No safe, effective therapy is yet available. Within the last few years, hydroxyurea has been used in an increasing number of sickle cell anemia patients. However, hydroxyurea is a chemotherapeutic agent with myelosuppressive effects and its long term safety is still unknown. An ideal agent would be one that is readily available, effective and safe even with chronic use. Based on previous data from this laboratory on sickle red blood cell metabolism, we have conducted a pilot study recently using L-glutamine as an oral agent. The four week open label study involving seven homozygous hemoglobin S patients showed promising results by demonstrating improvement in redox potential and decrease in chronic pain in all patients. In addition a subsequent 12 week study involving 4 patients showed significant decrease in the frequency of painful sickle crises. On the basis of these data we propose to expand the study of L-glutamine therapy for sickle cell anemia to a double blind study to observe objectively the effect of the amino acid in sickle cell anemia patients in terms of their clinical status and hematological parameters. Our long term goal is to establish the usefulness and safety of L-glutamine in therapy of sickle cell anemia. Our specific aims in this project are to determine the effect of oral L-glutamine on 1) sickle red blood cells at cellular and biochemical level, 2) clinical status of the sickle cell anemia patients including the incidence of painful crisis, narcotic requirement for acute or chronic pain, 3) sickle cell anemia patients' hematological parameters including hemoglobin, hematocrit, reticulocyte count,and hexokinase level, and 4) adverse effects attributable to L-glutamine. L-glutamine is an amino acid that has been used widely for other purposes and shown to be safe by others. It is also inexpensive and readily available. The pilot data are promising. This project will provide the pathophysiologic basis for the use of L-glutamine and will evaluate the efficacy of L-glutamine in the therapy of sickle cell anemia.