TTHX-1114: Engineered Growth Factor Has Potential to Treat Corneal Endothelial Deficiencies
The current standard of care for Fuchs and corneal endothelial dystrophies focuses on increasing the number and function of corneal endothelial cells via transplantation of donor tissue. In 2019, more than 35,000 endothelial transplant procedures were performed in the United States, and that number is on the rise. Corneal transplantation can effectively restore vision; however, postoperative recovery is challenging, and most patients undergo long-term chronic steroid therapy to minimize the risk of graft rejection.2,3
An alternative approach to the management of endothelial dystrophy is the stimulation of the existing corneal endothelial cells with an injection of a drug that will promote proliferation, migration, and regeneration. A novel drug under development by Trefoil Therapeutics with an engineered fibroblast growth factor (FGF) holds promise to help restore healthy endothelial function. An initial clinical trial has now been initiated in the United States in ten different locations.
TTHX-1114 is closely related to the molecule FGF-1, one of 22 naturally occurring FGFs. FGF-1 is the only FGF molecule that targets all seven FGF receptor isoforms; however, it has a short biological half-life due to its susceptibility to proteolysis and cysteine oxidation, making it unsuitable as a drug.
Trefoil Therapeutics has stabilized FGF-1 by making modifications to the structure of the protein to enable it to target the receptors in the eye that are responsible for endothelial cell regeneration. The compound is effective at much lower applied concentrations than native FGF-1, but qualitatively its biological activity is identical. TTHX-1114 is expected to have the same mechanism driven effects as FGF-1 with no unexpected activity.
It is expected that treatment with TTHX-1114 will require four to six injections in the eye, administered over a period of 6 to 12 months. At that point, we anticipate that patients’ endothelial cell counts will recover, and healthy endothelial function will be restored. The cornea represents 70% of the human visual system so we hypothesize that restoration of endothelial function should improve visual functioning.
Conclusion
Patients with Fuchs dystrophy who experience vision loss often defer treatment because it involves surgery. Having a nonsurgical option, such as treatment with TTHX-1114, could lead to earlier intervention and better visual outcomes for patients, while also avoiding the risk of transplant failure that occurs in a small percentage of patients.
1. Eye Bank Association of America. 2019 Statistical Report. https://eyelearn.restoresight.org/resources. Accessed June 25, 2020.
2. Allan BD, Terry MA, Price FW Jr, Price MO, Griffin NB, Claesson M. Corneal transplant rejection rate and severity after endothelial keratoplasty. Cornea. 2007;26(9):1039-1042.
3. Price MO, Scanameo A, Feng MT, Price FW Jr. Descemet’s membrane endothelial keratoplasty: risk of immunologic rejection episodes after discontinuing topical corticosteroids. Ophthalmology. 2016;123(6):1232-1236..
William B. Trattler, MD
• Director of Cornea, Center for Excellence in Eye Care, Miami
• Member, CRST Executive Advisory Board
• wtrattler@gmail.com
• Financial disclosure: Clinical advisory board (Trefoil Therapeutics)
