The aim of this project is to prevent blindness caused by corneal vascularization by reformulating a drug used in cancer treatment from oral to topical treatment (eyedrops).
We have identified variants in the platelet derived growth factor receptor beta (PDGFRB) gene in patients who loose vision early in life due to corneal vascularization (ingrowth of blood vessels into the clear cornea). Affected children develop the disease as early as two years of age. PDGFRB is a receptor tyrosine kinase that usually is only activated in certain biological processes, such as wound healing. Activation of PDGFRB is also seen in certain diseases, in particular cancer. The gene variants found associated with this disease cause PDGFRB to be constantly activated. This is a key factor in development of the corneal vascularization. We have shown that an approved drug used in cancer treatment reduce activation of PDGFRB in this condition. This opens up the possibility for precision-based treatment of the patients.
We have reformulated this drug from oral to topical eye drop treatment. We are currently examining the effect, and potential side-effects, of targeted treatment of PDGFRB in an animal model of the disease. If effective, the drops can be offered to patients on compassionate ground by the end of the project period.
We are also working towards obtaining orphan disease designation for the eye drops treatment.