Pete Coffey: Driving stem cells to the clinic
by Guest Author on 20 Feb 2014
Professor Pete Coffey, Professor of Cellular Therapies at the Institute of Ophthalmology, University College London, is an MRC-funded researcher who is developing a stem cell therapy for a degenerative eye condition that is the leading cause of blindness in UK adults. He spoke to Katherine Nightingale about the long road to the clinic.
Researchers seldom like to predict how long it might be before their discoveries are tested in patients. “At least five years” is a typical response, but one that should usually be taken with a pinch of salt. Research is complex, there are many obstacles to overcome, and some promising ideas never get anywhere near a clinic.
All the more surprising then that Pete Coffey gave himself and his team five years from 2007 to ready a stem cell therapy for a degenerative eye condition for clinical trials. And perhaps more surprising still — he’s done it.
The condition in question is age-related macular degeneration (AMD). Most people with AMD have the ‘dry’ form, which occurs when a carpet of cells behind the retina start to die. These retinal pigment epithelial (RPE) cells nourish the ‘seeing’ cells of the retina, as well as removing dead cells that would otherwise build up and cause damage. People with AMD gradually lose sight from a part of the retina called the macula, which is responsible for sharpness of vision in the centre of the visual field — the vision needed for reading, driving and recognising faces. There is no treatment for dry AMD.
But if everything goes to plan, Pete’s work will change this. His London Project to Cure Blindness, established in 2007 after a large donation from an anonymous individual, set itself the challenge of developing a stem cell therapy for dry AMD by the end of 2012. The ultimate aim is to replace the dying RPE cells before any damage is caused to the seeing cells, therefore keeping vision intact.
Through the hoops
Pete and his team have developed a way to make RPE cells from human embryonic stem cells (hESCs) in the lab. They use a particular hESC line called Sheff-1 which was created by University of Sheffield researcher Harry Moore in 2004 with MRC funds.
These RPE cells can stall loss of vision in rats. When implanted into the eyes of the rather grandly named Royal College of Surgeons rat (which goes blind after eight weeks because of a mutation in its RPE cells) the rats retained their vision.
But getting to a point where you’re ready to transplant stem cells into patients is much more of a challenge. The trial will be only the fourth in the world of cells derived from hESCs.
Given that this is relatively uncharted territory, “We’ve really had to come up with every step of the process ourselves,” says Pete. “That means things like testing the cells in animals to make sure that they don’t produce tumours, and producing the cells to the required, clinical-grade standard — for which we had to build our own facility.”
Actually getting the cells into the eye has also been a challenge. Pete and his team had to develop a membrane made from clingfilm-thin, super-strong material, onto which they seed the cells. This is then rolled up and delivered into the back of the eye by a specially designed surgical tool.
The team also had to perfect a new surgical technique, which has been tested on around 40 pigs. “The pig eye is the same size as a human eye, so we did the exact operation on pigs to ensure that it would work successfully. The operation will only take about 45 minutes and could be considered as an outpatient procedure,” says Pete.
And to tell whether the cells are working once they are in the eye, Pete and his team have also used MRC funds to develop imaging techniques that look at their survival and function after transplant.
Going to trial
So far, the team has developed and checked the manufacturing process for the cells, and the technique to deliver them into the eye. They have also received ethical and regulatory approval to conduct a study at Moorfields Eye Hospital in the United Kingdom.
The next step in the partnership is to start a Phase 1/2A study to evaluate the safety and feasibility of the technique, and whether it works in people with the ‘wet’ form of AMD who have experienced a recent rapid decline in their vision. Wet AMD progresses much faster than dry AMD, and is caused by new blood vessels growing in the wrong place and damaging the macula. The partners are in the process of producing the cells and expect patients to enter the clinic as soon as is feasible.
It won’t all be plain sailing. Even if the transplants work, no one really knows to what extent the patient’s immune systems will reject them. It might be that in the future, RPE cells made from a patient’s own cells — via so-called induced pluripotent stem cells — will be the best source for transplant.
Driving to the clinic
So does Pete have any regrets on setting himself the five-year limit? “Well, I’m not going to do it again — I’ve gone completely grey since starting the project!” he says.
But he has learned two lessons: join forces with an industry partner, and work in parallel. The London Project formed a collaboration with Pfizer in 2009, giving Pete access to their expertise. “There’s no way an academic scientist like me could do this alone,” he says.
Similarly, the usual sequential style of academic research doesn’t suit a drive for the clinic.
“We could only do this so fast because we were developing each strand of work at the same time. If we’d done everything in separate steps, we’d be nowhere near where we are today,” he concludes.