Stem Cell Graft Engineering to Treat Sickle Cell Disease

描述(申请人提供)：镰状细胞病(SCD)是一种红细胞(RBC)异常，在美国大约有72,000人受到影响，或者说大约每500名非洲裔美国人中就有一人受到影响。按照目前的治疗方法，到40岁时，美国的死亡率为50%。SCD是一种慢性、衰弱的疾病，与频繁的疼痛危象、急性胸部综合征、中风和肾功能衰竭有关。因此，患者需要频繁住院，并经历缺勤。迄今为止，SCD的唯一治愈方法是骨髓移植(BMT)。然而，目前与消融性骨髓移植相关的发病率和死亡率限制了该方法的广泛应用。此外，对完全匹配的捐赠者的要求将骨髓移植限制在只有17%的候选人。我们开发了一种设计骨髓移植的方法，以避免骨髓移植的主要并发症：移植物抗宿主反应性(GVHD)；移植物失败；以及需要完美匹配。我们的方法优于目前的治疗方法，因为它涉及一种专利过程，丰富了专利促进细胞(FC)和干细胞，但去除了产生GVHD的细胞。在这项提案中，我们将使用这种已经被证明对白血病患者有效的FCRx产品，用于治疗SCD患者。在第一阶段，我们将开发一种非清髓性条件作用方法来建立20%的供者嵌合体。明确的终点将是植入和生产正常的红细胞。从长远来看，我们将开发和销售一种质量受控/质量有保证的FDA批准的骨髓产品(SCD FCRx)来治疗SCD患者。我们的平台技术将作为FDA批准的生物服务提供给世界各地的医院系统。这种治疗方法可以扩展到其他血液疾病，包括地中海贫血。该公司和该大学的互补结构和专业知识为这一联合努力提供了很好的条件。该公司将制定生产和营销该产品的战略，而该大学将进行临床试验，并在其事实认可的细胞处理设施中处理骨髓。

DESCRIPTION (provided by applicant): Sickle Cell Disease (SCD) is an abnormality of red blood cells (RBC) that affects approximately 72,000 people in the United States, or approximately 1 in every 500 African-Americans. With current therapies, the mortality in the United States is 50 percent by age 40. SCD is a chronic, debilitating disease associated with frequent painful crises, acute chest syndrome, stroke, and renal failure. As a result, patients require frequent hospitalizations and experience absenteeism from work. The only cure for SCD to date is bone marrow transplantation (BMT). However, at present the morbidity and mortality associated with ablative BMT has limited the widespread application of this approach. Moreover, the requirement for a perfectly matched donor has limited BMT to only 17 percent of candidates. We have developed an approach to engineer a bone marrow graft to avoid the major complications of BMT: graft-versus-host reactivity (GVHD); graft failure; and the need for perfect matching. Our approach is superior to current therapies because it involves a proprietary process that enriches for patented facilitating cells (FC) and stem cells but removes GVHD-producing cells. In this proposal we will utilize this FCRx product, already demonstrated to be effective for treatment of leukemic patients, for treatment of patients with SCD. In phase I, we will develop a nonmyeloablative conditioning approach to establish 20 percent donor chimerism. The well defined end point will be engraftment and production of normal RBC. In the long term we will develop and market a quality controlled/quality assured FDA-approved bone marrow product (SCD FCRx) to treat individuals with SCD. Our platform technology will be provided to hospital systems worldwide as an FDA-approved bioservice. Such a treatment approach could be expanded to other blood disorders, including thalassemia. The complimentary structure and expertise of the company and the University lends itself nicely to this joint effort. The company will develop a strategy to produce and market the product while the University will conduct the clinical trial and process the marrow in its FACT-accredited cell processing facility.