First in human phase I / II clinical trial of RAFT for aniridia related keratopathy.

The cornea on the front surface of the eye is our window to the world. If transparency is compromised, visual impairment and even blindness can occur. Aniridia is a rare blinding disease (1:100,000 incidence) caused by a mutation in PAX6 which is one of the genes responsible for development and healthy function of the eyes. Aniridia-related keratopathy (ARK) manifests as persistent, chronically painful defects of the outer epithelial layer of the cornea called the epithelium. Blood vessels grow into the cornea and scarring also occurs, both of which obstruct vision. ARK induced light sensitivity can lead to social exclusion. The cause of these symptoms is related to the inability of the mutated limbal epithelial stem cells (LESC), stromal cells and tissue to maintain normal corneal epithelium. Current treatments include whole donor tissue transplantation and cultured LESC therapy which have both shown poor long-term outcomes. Since stem cells require support from neighbouring cells and proteins in their environment, transplanting cultured LESC alone may not be sufficient to preserve / improve patient vision. An optimal ARK treatment would include transplantation of both healthy LESC and a stroma (corneal support tissue) populated with stromal cells. Our proposed solution utilises our patented technology known as RAFT (Real Architecture for 3D Tissues) in which LESC and stromal cells are cultured together in a transplantable collagen matrix (artificial tissue). We are able to make this tissue in compliance with the required regulations which are known as Good manufacturing practise, or GMP for short, in our clinical cell therapy production laboratory. Pre-clinical safety studies supports us moving forward to a first in human study. In this project we will undertake 1) full GMP protocol validation for RAFT in our Cells for Sight licensed manufacturing facility, 2) write and submit all of the documentation required to obtain regulatory approval for a clinical trial and 3) proceed to first in human RAFT transplantation studies in patients with ARK. In this phase I/II clinical trial we will perform RAFT transplantation in one eye of 21 ARK patients to assess RAFT safety and preliminary efficacy. The outcome measures will include restoration of a normal corneal epithelium without any defects, blood vessel ingrowth or scarring. If successful, this therapy could provide a much-needed solution for patients with ARK and also act as a springboard for the development of RAFT for other blinding eye diseases.