Therapy for Fuchs Endothelial Corneal Dystrophy

Fuchs内皮性角膜营养不良(FECD)是以角膜内表面单层内皮细胞进行性变性为特征的疾病。细胞外基质聚集在角膜基质和后弹力膜的内皮细胞层之间，导致角膜水肿、光学质量丧失和视力下降。FECD进展缓慢，直到内皮层严重退化，患者才会寻求治疗。移植是目前唯一的治疗方法。然而，供体角膜供应有限，手术并发症可能很严重，由于内皮营养不良而进行的移植有较高的长期失败率。一种更理想的治疗方法将完全避免移植的需要。 成纤维细胞生长因子(FGFs)在体外可以刺激人角膜内皮细胞的增殖和迁移，在体内具有再生治疗的潜力。然而，野生型成纤维细胞生长因子作为治疗药物的应用受到稳定性和药代动力学的限制。主要合作者已经开发出一种工程化成纤维细胞生长因子(EFGF)，该因子在临床前研究中显示出更好的稳定性和有效性。TRND的科学家已经开发了一种用于eFGF的生产工艺，并已经完成了使IND成为可能的研究，从而能够提交IND并启动第一阶段临床研究。

Fuchs endothelial corneal dystrophy (FECD) is marked by progressive degeneration of the monolayer of endothelial cells on the inner surface of the cornea. Extracellular matrix accumulates between the corneal stroma and the endothelial layer at Descemets membrane, leading to corneal edema, loss of optical quality, and decreased vision. FECD is slowly progressive, and patients do not seek treatment until the endothelial layer is badly degenerated. Transplantation is the only current treatment. However, donor corneas are in limited supply, surgical complications can be significant, and transplants due to endothelial dystrophy have a higher long-term failure rate. A more optimal therapy would avoid the need for transplantation altogether. Fibroblast growth factors (FGFs) have been shown to stimulate proliferation and migration of human corneal endothelial cells in vitro and have the potential to be regenerative therapies in vivo. However, the application of wild type FGFs as therapeutics is limited by poor stability and pharmacokinetics. The lead collaborators have developed an engineered fibroblast growth factor (eFGF) that has demonstrated improved stability and potency in preclinical studies. TRND scientists have developed a production process for eFGF and have completed IND-enabling studies to enable filing of the IND and initiation of Phase 1 clinical studies.