Diagram of virus particle used for gene therapy

Gene therapy for defects in the Retinal Pigment Epithelium (RPE)
RP can be caused by defects in either of two cell types: the photoreceptor cell or the retinal pigment epithelium (RPE). The RPE sits behind the photoreceptor cells in the eye and is responsible for supporting the photoreceptor cells. It provides nutrients and oxygen and removes waste from the photoreceptor cells and it recycles the important chemicals in that waste back to the photoreceptor cells. When the RPE is not functioning properly, the photoreceptor cells are not able to obtain essential nutrients or chemicals and, although they are not defective, they stop functioning or die.

RPE defects that cause RP are relatively rare, but with respect to treatment these diseases have 2 advantages over other forms of RP.

1. Because the defect is in the RPE, the photoreceptor cells are inherently healthy and they should survive if the RPE can be repaired
2. The RPE is relatively easily treated. Whereas it can be difficult to treat sufficient numbers of photoreceptor cells, the RPE takes up a lot of virus

We have successfully treated two animal models of RPE defects. The first model is a strain of rats that have a gene defect that prevents the removal of photoreceptor cell waste by the RPE. In these animals, the waste material accumulates between the photoreceptor cells and the RPE. As a result, the supply of nutrients and oxygen to the photoreceptor cells is interrupted and these cells die. Following replacement of the faulty gene, we found a decrease in the amount of accumulated waste and a prolonged survival of the photoreceptor cells.

The second RPE defect we have treated in animals was a form of Leber’s congenital amaurosis (LCA2), caused by a defect in a gene called RPE65. This defect results in the inability of the RPE to recycle a chemical that is essential for the capture of light. In this disease, the photoreceptors survive well, but because of the lack of this chemical, they cannot function. After treating mice with this defect we could show that the photoreceptors are functioning by measuring electrical responses to light. Before the mice were treated, no such responses were present. This success convinced us to treat a strain of dogs with the same defect. In the dogs we could not only show electric responses, but we could also detect a clear improvement in their ability to walk through a maze. These experiments provide definitive proof of improved vision following gene therapy.

After the successful treatment of mice and dogs, we have received approval from the regulatory authorities to start a clinical trial of gene therapy in 12 patients with mutations in this gene

This page last modified 18 December, 2012 by xxx