Phase I of the London Project to Cure Blindness was a 5 year research project that aimed to develop a stem cell based therapy for Age-related Macular Degeneration (AMD). The transplanted stem cells would replace damaged natural cells and restore sight, prevent blindness and improve sufferers’ quality of life. Phase I has progressed as planned and the major pre-clinical work is completed. The regulatory requirements are currently being addressed for an application for a clinical trial in 2012. We are now moving into Phase II of the study in which we hope to create individualized stem cells from each patient that has AMD. We will use the patients’ own stem cells, taken from a blood sample or skin snip, to make personalized RPE cells for transplantation. These cells will have the advantage of being a perfect match between the patient and the transplanted cells.
Our approach in this project is to replace retinal pigment epithelium cells (RPE). These are a sheet of cells at the back of the eye, under the retina, supporting the rods and cones that are critical to normal sight. When these RPE cells are damaged they are thought to lead to AMD. The damaged RPE cells will be replaced by 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 taken from each patient. The stem cells are grown into healthy RPE cells using techniques developed by the Team. These RPE cells will then be transplanted into the patient on a specially engineered patch using a new delivery device developed by the London Project.
Another 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. All of the Phase II studies involve investigation of new imaging technology, creation of new surgical techniques and development of new instruments
The project came into existence in June 2007 following a major philanthropic donation. The Macular Disease Society then made The London Project the focus of their annual appeal, which resulted in a donation of £100k at an extremely critical stage. In 2008, the US-based Lincy Foundation also went on to make a substantial donation. In 2009, the project appeared on the front page of the Sunday Times after an agreement was announced with the pharmaceutical company, Pfizer. The agreement is the first of its kind for a stem cell therapy and is believed to mark a new stage in the evolution of this technology and its clinical application. Prof Pete Coffey said “this important partnership will help to drive the science forward and ensure that the cells can be manufactured to the standards that required for clinical trials”. Pfizer’s expertise in clinical trials and extensive experience in obtaining approval from regulators will also prove to be invaluable to the success of the project.
Furthermore, we have received hundreds of extremely generous donations from members of the public who have either read about the project, are sufferers themselves or have a member of the family who is affected by this disease. The public support and general level of enthusiasm shown for the project has been truly outstanding and we have been delighted to hear from many sufferers who have shared their stories and expressed their thanks for the hope that the project has given them.
Phase II funding was initiated with a generous philanthropic gesture by Storholm Racing that linked the project to their Le Mans racing team. This led to The London Project’s message travelling at incredible speeds around Silverstone in the UK and the Petite Le Mans in Atlanta, Georgia, USA. The sponsorship also helped raise an initial donation of £30k from a charity auction. A further £155k has been received from three philanthropic donations. In 2011 The London Project’s scientific lead, Prof Pete Coffey, became the first recipient of the New York Stem Cell Foundation’s Robertson Prize, awarded annually for extraordinary achievement in translational stem cell research. The prize was accompanied by a £125K donation to the project. This latter donation was generously matched with a further £125k from the Michael Uren Foundation. Furthermore, we continue to be fortunate enough to receive many individual donations from members of the public who have either read about the project, are sufferers themselves or have a member of the family who is affected by this disease. The public support and general level of enthusiasm shown for the project has been truly outstanding and we have been delighted to hear from many sufferers who have shared their stories and expressed their thanks for the glimmer of hope that the project has given them.
We have the possibility of a further £900k from applications and projects for this year. As such we remain motivated to continue this work in order to acknowledge the variety of donors and philanthropists who have supported us throughout this endeavour.
Research we have conducted to date
A programme of proof-of-concept clinical trials was 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. Firstly, we investigated the use of adult stem cells but results showed that they lacked a number of components required to produce healthy RPE cells. As a result we had to look for an alternative source of cells. 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 part of the research has been to create new operations and technology to deliver the stem cells. This new technology makes it possible for surgery to be performed on a day case basis with the operation itself potentially taking less than an hour to complete. It is also clear that the quality of the cells transplanted is highly superior to those taken from the aged, diseased eye as in the original clinical trials.
Human clinical trials
We have now completed the major safety studies that have been outlined by the regulators, prior to clinical trials. Hence, we are on track to commence human clinical trials in 2013. However, it is important to stress that the exact launch date of the trials is very much in the hands of the UK regulatory bodies, provided that they are fully satisfied with the safety study data that we have submitted.
The nature of the project and the fact that it will be one of the first studies ever using embryonic stem cells for therapy means there will be strict criteria for patient inclusion in the initial trials. Currently there is no list on which patients can record their interest in trials. Once the initial trials are approved by the regulatory bodies they will take place at Moorfields Eye Hospital from where patients will be recruited.
Please note: the clinical trials are expected to start in 2013. Unfortunately there is no list on which patients can record their interest in trials at present.