New Therapies on the Horizon for Corneal Endothelial Regeneration

The need for an effective pharmaceutical therapy for treating corneal dystrophy is well recognized by cornea specialists, with 98% saying in a recent survey that they would use such a drug on patients suffering from Fuchs dystrophy. Now new research directed at ways to regenerate the corneal endothelial layer is yielding some promising results and may soon produce such a therapy.

Acceleration of regeneration of the endothelial layer by eFGF-1 treatment in the rabbit. The green lines are the outlines of the endothelial cells of the cornea. Treatment with eFGF-1 results in earlier regeneration of the corneal endothelium, as seen at the ‘3 days’ time point.

In one such approach,Trefoil Therapeutics of San Diego, CA has taken a naturally occurring growth factor, FGF-1, that is part of the normal development of the cornea and supercharged it using molecular biology techniques. Also known as acidic FGF,it is a potent and broad spectrum signaling agent that functions by binding to high affinity transmembrane receptors present on corneal cells and is used by the body to promote repair and regeneration of damaged tissues. In collaboration with researchers at Florida State University, Trefoil has produced engineered FGF-1 (eFGF-1) proteins that are about 100 fold more potent than the normal FGF-1.

The goal of this research is to create a drug that could be used to regenerate the corneal endothelial layer without the need for surgery. In order to specifically target the corneal endothelial cell layer, the drug is intended to be administered by injection into the space between the cornea and the iris, where it will have direct access to the compromised corneal endothelial layer.

In laboratory studies including cell culture experiments and rabbit models of corneal dystrophy, Trefoil’s eFGF-1 molecules stimulate corneal endothelial cells to re-grow and accelerate the regeneration of the corneal endothelium (See Fig.). Data presented at the Association for Research in Vision and Ophthalmology (ARVO) meeting in 2015 suggested that the growth rate of human corneal endothelial cells could be more than doubled by application of an eFGF-1.

While this work is very promising, as with all new therapies this drug must pass a series of tests for safety and efficacy before being available to patients. The next steps in development are a series of safety studies in animals followed by clinical studies to evaluate the safety and potential efficacy. The first clinical studies are not anticipated to begin until late in 2017.

In addition to this approach, there are research efforts underway in at least two laboratories to grow corneal endothelial cells from stem cells in order to transplant these healthy endothelial cells into patients. Clinical trials with these cells have begun in Japan and are likely to start soon in the US.

The progress of research from the laboratory towards clinical testing reflects the hard work of both scientists in the lab and patients and clinicians advocating for corneal research. It is hoped that progress continues and new and effective treatments are on the way.

David Eveleth, PhD, Trefoil Therapeutics, and William Stewart, MD, PRN PharmaFarm.

Acceleration of regeneration of the endothelial layer by eFGF-1 treatment in the rabbit. The green lines are the outlines of the endothelial cells of the cornea.
Treatment with eFGF-1 results in earlier regeneration of the corneal endothelium, as seen at the ‘3 days’ time point.