AMD-FCRx to Restore Damaged Pigment Epithelium

AMD-FCRx 可恢复受损的色素上皮

• 批准号: 6991727
• 负责人: SUZANNE T ILDSTAD
• 金额: $ 35.51万
• 依托单位: REGENEREX, LLC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6991727
• 关键词: cell differentiation; cell migration; cell proliferation; eye surgery; hematopoietic stem cells; hematopoietic tissue transplantation; laboratory mouse; macular degeneration; retinal pigment epithelium; stem cell transplantation; therapy design /development; visual photoreceptor

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. The hallmark of the disease is retinal pigment epithelial (RPE) dysfunction with subsequent death of the foveal photoreceptors. Hematopoietic stem cells (HSC) have been demonstrated to repair damaged tissues including heart muscle and nerve under selected conditions. Allogeneic RPE transplantation has been attempted to restore the damaged RPE. However, allogeneic RPE cells do not attach to senescent Bruch's membrane efficiently, and do not efficiently repair the defect. Furthermore, rejection occurs after allogeneic adult RPE transplantation unless immunosuppression is employed. Thus, the development of a syngeneic HSC product (AMD-FCRx) to treat AMD and avoid the need for systemic immunosuppression would be a major advance. We were the first to discover CD8+/TCR- graft facilitating cells (FC), a novel cell in bone marrow that significantly enhances HSC engraftment in syngeneic recipients. FC express SDF-1, a critical chemokine for HSC homing, and CXCR4, its unique receptor that is also present on HSC We have strong preliminary data to show that FC enhance homing of HSC to damaged RPE. As such, FC may play a critical role in HSC-mediated repair of damaged RPE. In phase I of this application we will define the optimal composition of HSC and FC for transplantation to replace damaged RPE. Specifically, we will optimize strategies to promote homing of HSC to areas of RPE damage or loss, attach to normal Bruch's membrane, proliferate and fill in the defect created, and differentiate into mature RPE cells. These studies will lay the groundwork for Phase II in which the AMD-FCRx product will be tested in a more rigorous model of AMD and then translated into a phase I clinical protocol. Regenerex, LLC has been incorporated to commercialize the benefits of bone marrow graft engineering technologies for treatment of blood disorders and tissue repair. We have assembled a highly talented team with expertise in ophthalmology, stem cell biology, and transplantation. A unique collaboration between the Louisville Medical Center Development Corporation, Jewish Hospital, the State of Kentucky, and the University of Louisville to develop a biomedical incubator has allowed Regenerex, LLC to move into office space located at 201 East Jefferson Street. Our long-term goal is to exploit the potential of the facilitating cell by marketing a well-defined HSC cellular therapeutic product for worldwide distribution to treat AMD. Regenerex is a woman-owned business in Kentucky, an EPSCoR state.

描述（由申请人提供）：视网膜相关性黄斑变性（AMD）是西方世界失明的主要原因。该疾病的标志是视网膜色素上皮（RPE）功能障碍，随后中心凹光感受器死亡。造血干细胞（HSC）已被证明可以在特定条件下修复受损组织，包括心肌和神经。同种异体RPE移植已被尝试恢复受损的RPE。然而，同种异体RPE细胞不能有效地附着到衰老的布鲁赫膜上，并且不能有效地修复缺陷。 此外，除非采用免疫抑制，否则同种异体成人RPE移植后会发生排斥反应。因此，开发同源HSC产品（AMD-FCRx）来治疗AMD并避免对全身免疫抑制的需要将是一个重大进展。我们是第一个发现CD 8 +/TCR-移植促进细胞（FC），一种新的细胞在骨髓中，显着提高造血干细胞植入同基因受体。FC表达SDF-1（HSC归巢的关键趋化因子）和CXCR 4（也存在于HSC上的其独特受体）。我们有强有力的初步数据表明FC增强HSC归巢至受损RPE。因此，FC可能在HSC介导的受损RPE修复中发挥关键作用。在本申请的I期，我们将确定HSC和FC的最佳组合物，用于移植以替代受损的RPE。具体来说，我们将优化策略，以促进HSC归巢到RPE损伤或丢失的区域，附着到正常的Bruch膜，增殖并填充所产生的缺陷，并分化为成熟的RPE细胞。这些研究将为第二阶段奠定基础，其中AMD-FCRx产品将在更严格的AMD模型中进行测试，然后转化为第一阶段临床方案。 Regenerex，LLC已被纳入商业化的好处骨髓移植工程技术治疗血液疾病和组织修复。我们已经组建了一个在眼科，干细胞生物学和移植方面具有专业知识的高素质团队。路易斯维尔医疗中心发展公司、犹太医院、肯塔基州和路易斯维尔大学之间的一项独特合作，开发了一个生物医学孵化器，使Regenerex，LLC搬进了位于东杰斐逊街201号的办公空间。我们的长期目标是通过销售一种定义明确的HSC细胞治疗产品来开发促进细胞的潜力，在全球范围内销售以治疗AMD。Regenerex是一家位于EPSCoR州肯塔基州的女性企业。