Phase1/2a Clinical Trial of RPESC-derived RPE Transplantation as Therapy for Non-exudative Age-related Macular Degeneration

RPESC 衍生的 RPE 移植治疗非渗出性年龄相关性黄斑变性的 1/2a 期临床试验

• 批准号: 10044560
• 负责人: Jeffrey H Stern
• 金额: $ 20.06万
• 依托单位: REGENERATIVE RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2021-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10044560
• 关键词: Adult; Age related macular degeneration; Amendment; Animal Model; Atrophic; Blindness; Caring; Cell Differentiation process; Cells; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Collection; Communication; Conduct Clinical Trials; Consent; Consent Forms; Cyclic GMP; Data; Data Collection; Elderly; Engraftment; Enrollment; Ensure; Eye; Genotype; Grant; Institutes; Institutional Review Boards; Interruption; Intervention; Investigation; Maintenance; Manuals; Manuscripts; Measures; Medical; Michigan; Modeling; Modification; Monitor; Nature; Nonexudative age-related macular degeneration; Outcome; Outcome Assessment; Pamphlets; Participant; Pathogenesis; Patient Recruitments; Patients; Phase; Phenotype; Pluripotent Stem Cells; Procedures; Protocols documentation; Rattus; Regenerative Medicine; Replacement Therapy; Reporting; Research Personnel; Retina; Review Committee; Risk; Safety; Site; Source; Specialist; Stem Cell Research; Stem cell transplant; Structure of retinal pigment epithelium; Supporting Cell; Surgeon; Time; Tissues; Translating; Translations; Transplantation; United States National Institutes of Health; Universities; Vision; Work; adult stem cell; aging population; base; catalyst; clinical research site; college; data management; design; dissemination trial; early phase clinical trial; effective therapy; epithelial stem cell; experience; experimental study; eye center; improved; nerve stem cell; novel therapeutics; operation; post intervention; pre-clinical; preservation; progenitor; programs; quality assurance; recruit; repaired; retina transplantation; retinal progenitor cell; sound; stem cell biology; stem cells; transcriptome; transcriptomics; trial design; tumor; tumor growth

Project Summary/Abstract Age-related macular degeneration (AMD) is a major cause of blindness in our aging population. Early AMD pathogenesis involves atrophy of the retinal pigment epithelium (RPE) with accompanying loss of retinal function and vision. Although therapy is available for exudative (wet) AMD, an effective treatment is not available for the more common non- exudative (dry) AMD form. Pluripotent stem cell (PSC)-derived RPE (PSC-RPE) transplantation has shown promise for AMD in early clinical trials. Due to the highly proliferative and plastic nature of PSC, however, extensive differentiation to RPE is needed prior to transplantation to avoid tumor growth and genotype instability inherent to the PSC source. We discovered an adult RPE stem cell (RPESC) with restricted proliferative and lineage potential. RPESC-derived RPE (RPESC- RPE) do not form tumor enabling transplantation of less differentiated RPE at the progenitor stage. We found that transplanted RPE progenitor cells were more effective than highly differentiated progeny at vision rescue in the Royal College of Surgeons rat model of AMD. RPESC-RPE differentiated for 4 weeks into an intermediate RPE progenitor stage rescued vision more effectively than cells differentiated for 8 weeks into the mature RPE phenotype. This improved efficacy combined with lack of tumorgenicity provides compelling rationale for the proposed Phase 1/2a clinical trial of RPESC-RPE transplantation as therapy for dry AMD. Experienced clinical trial teams have been assembled at the University of Michigan Kellogg Eye Center (KEC) and Stanford University. The KEC team includes a vitreoretinal surgeon experienced in stem cell research who will recruit, perform interventions, and manage participant care. Another retinal specialist will direct post-intervention assessment at the KEC Clinical Research Center, and a senior KEC retinal specialist will serve as on-site medical monitor. A clinical trialist highly experienced in early phase ophthalmic trials will provide regulatory, design and statistical support. The Neural Stem Cell Institute (NSCI) and the Stanford University Byers Eye Institute will work with KEC to provide scientific and clinical guidance for the proposed trial. Single cell transcriptomic analyses generated at NSCI will be correlated with clinical outcomes, which will contribute to the recognized need for improved cell product identity and potency measures in regenerative medicine generally. We propose to combine a strong program in stem cell biology with an experienced team in the conduct of ophthalmic clinical trials Sound clinical trial conduct aims to produce reliable outcomes results to evaluate RPESC-RPE progenitor cell transplantation as therapy for dry AMD. Outcomes will be correlated with product identity and potency measures at the single cell level. Completion of the proposed work will improve understanding of RM product characterization and advance a unique type of adult stem cell to replace RPE for dry AMD patient benefit.

项目总结/文摘