Our aim in this project is to replace damaged and diseased retinal cells that lead to Age-related Macular degeneration with healthy cells that are grown from stem cells. Stem cells are cells found within the body that can reproduce infinitely and turn into any cell of the body. Potentially you need only one healthy stem cell to replace every cell and cell type in the body.
The first cell type we are aiming to replace is the retinal pigment epithelium cell (RPE). These cells form a thin sheet lining the inside of the eye, under the retina. (?rods and cones) A healthy RPE layer is critical to normal sight. When these RPE cells are damaged or lost they are thought to lead to AMD. We aim to replace the damaged RPE cells with a sheet of RPE cells created from stem cells. In phase I the stem cells that we have used are human embryonic stem cells (hES) while in Phase II these will be stem cells derived from each patient, allowing an individualised cell replacement and a near perfect match for the patient. The RPE cell sheets will be transplanted into the patient on a specially engineered patch using a new delivery device developed by the London Project Team.
A programme of proof-of-concept clinical trials were conducted at Moorfields Eye Hospital in 2007 - 2008 using RPE cells from the patient’s own eye via two methods; autologous transplantation and macular translocation. These trials enabled the project team to demonstrate that placing “healthy” RPE cells under the damaged area of the macular can prevent blindness and restore sight. However, the complexity of the surgery and complications associated with having two lengthy operations did not allow for this to be a viable treatment for the number of AMD patients that would need to be treated.
The London Project team then began to look into the possibility of using stem cell technology to replace the diseased cells in AMD and get the same beneficial effect as in the proof of principle operations. Human Embryonic Stem cells (hES) were considered the best option at the time. It was found that, given the right conditions, hES could be transformed into healthy, fully functioning RPE cells. As a prelude to clinical trials we have been able to successfully demonstrate that visual function can be restored in an animal model of AMD.
A further longer term and important arm of the project has been to develop the technology by which stem cells can be transformed into photoreceptors (primarily cones and rods) and transplanted into patients. It is believed that the photoreceptors are lost after the RPE have degenerated. The clinical application of this component of the project is for cases where the disease has been present for a number of years and the vision lost.
So far we have been able to grow RPE cells from both human embryonic stem cells (phase I) and cells from specific individuals (Phase II). These RPE cells grown from stem cells not only appear to behave like normal RPE when grown into sheets but also have the gene expression profile that is identical to natural human RPE. This is very important as any RPE based transplantation strategy designed to treat AMD must show that the transplanted cells are faithful copies of the cells to be replaced.
Phase I of the project has reached the stage where the major safety experiments are completed and we are preparing for the final submission to the regulatory authorities for a clinic trial in 2012. The Phase II studies have reached their proof of principle stage and we are now embarking on a fund raising exercise to raise the £ 5 million required to make personalised stem cells a reality for transplantation in AMD.