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Therapeutics for Rare and Neglected Diseases

Therapy for Fuchs Endothelial Corneal Dystrophy

Fuchs endothelial corneal dystrophy (FECD) is a degenerative disease of the eye. The front surface of the eye, called the cornea, helps regulate vision by focusing light onto the lens. FECD affects the thin layer of cells at the back of the cornea, which progressively become damaged and die. As these cells are lost, the cornea retains excess fluid, resulting in loss of optical quality and decreased vision. Most patients are diagnosed with FECD only after significant numbers of corneal cells have been lost, and the only treatment for advanced disease is corneal transplantation. The lead collaborators have developed a growth factor therapy that aims to halt, and potentially reverse, the degeneration of endothelial cells. The purpose of this project is to support further pre-clinical development and enable clinical trials.

Scientific Synopsis

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 Descemet’s membrane, leading to corneal edema, loss of optical quality, and decreased vision. FECD is slowly progressive, and typically 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 FGF that has demonstrated improved stability and potency in pre-clinical studies.

Lead Collaborator

Trefoil Therapeutics, LLC, San Diego
David Eveleth, Ph.D.

Public Health Impact

FECD is a progressive, degenerative disease of the eye that can only be treated by corneal transplantation. Although outcomes of transplantation are generally good, failure rates in FECD patients are significant. A non-surgical therapy that can halt the degeneration — and potentially regenerate lost endothelial cells — would be transformative for this population.

Outcomes

The TRND project team has conducted a rigorous gap analysis to determine the project plan. TRND scientists are developing a production process, conducting pre-clinical safety studies, and manufacturing and formulating clinical-grade material. Completion of these studies will enable the lead collaborator to submit an Investigational New Drug application to the Food and Drug Administration.

Last updated: 09-06-2017
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