ORAL L GLUTAMINE THERAPY FOR SICKLE CELL ANEMIA

描述：镰状细胞贫血是最常见和最具破坏性的贫血之一。 发病率和死亡率高的遗传性疾病， 非裔美国人的遗产。 目前还没有安全有效的治疗方法 available. 在过去的几年中，羟基脲已被用于 镰状细胞性贫血患者的数量不断增加。 然而，羟基脲是一种 具有骨髓抑制作用的化疗剂及其长期应用 安全性仍然未知。 一个理想的代理人将是一个容易 即使长期使用也是有效和安全的。 基于先前的数据 从这个实验室的镰状红细胞代谢，我们已经进行了 最近一项试验性研究使用L-谷氨酰胺作为口服药物。 四周 涉及7名纯合子血红蛋白S患者的开放标签研究显示， 通过证明氧化还原电位的改善和 减少所有患者的慢性疼痛。 此外，随后的12周 一项涉及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 谷氨酰胺治疗镰状细胞性贫血双盲研究 客观观察氨基酸对镰状细胞贫血的疗效 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）镰状细胞贫血的临床状态 包括患者疼痛危象的发生率、麻醉药的需要量、 急性或慢性疼痛，3）镰状细胞性贫血患者的血液学 参数包括血红蛋白、红细胞压积、网织红细胞计数，以及 己糖激酶水平，和4）归因于L-谷氨酰胺的副作用。 L-谷氨酰胺是一种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， available. 试点数据很有希望。 该项目将提供 使用L-谷氨酰胺的病理生理学基础，并将评估 谷氨酰胺治疗镰状细胞性贫血的疗效

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.