Dr John Sinden - chief scientific officer at ReNeuron Ltd, a company researching stem cells and possibilities for reversing cell damage in the brain. ReNeuron's work has demonstrated that injecting stem cells into the brains of mice can reverse the effects of stroke.

Could you explain a little about your company and the research that you do?
ReNeuron is a company in Guildford in Surrey, set up originally in King's College in London. It is based on the technology of generating neural stem cell lines that could be developed as products for treating major neurodegenerative diseases, particularly those in the elderly.

What are stem cells?
Stem cells are the first product of conception, so sperm meets egg, generates initially a single cell then a ball of cells, and then you have the beginnings of a human being. So stem cells are the early cells that are constantly dividing and gradually throwing off cells that are going to make up our bodies, our brains. The important thing is not only are they important in the whole process of development, it appears that their nature is a regenerative cell, so they are capable throughout life of regenerating all of our tissues, by actually inducing our natural cells to become alive again if there's any damage that occurs.

How did ReNeuron come about?
Well, we started with a stem cell line that we generated from mice, and we used it as a source of cells for transplantation purposes for animals that had a specific kind of damage. We injected the stem cell line near to the damage and what surprised us is that the cells actually migrated into the area of damage and when they got there they differentiated, that is, they made the right kind of cell that was missing in the brains of those animals. That was an important discovery because nobody had ever shown that before with any tissue system. So we were able to patent that then set up a company which was really directed at developing stem cell lines that could be available, as it were, off the shelf to neurosurgeons or to surgeons for the purposes of injecting into patients that had suffered some kind of damage.

Could you describe further what your research has discovered?
If you take the example of a stroke, it is a massive amount of damage on one side of the brain. What we've found is that if we take one of our stem cell lines and we inject it, we can even inject it on the opposite side of the brain to where the damage is, the cells actually cross over on the telephone exchange that connects the 2 sides of the brain, move into the damaged area and make new cells that are typical in the region that where the damage is. But they also act along with a process that seems to be naturally occurring within the stroke brain. There seems to be a natural attempt by the brain after a stroke to try and send out signals, to try and recover itself, and we've actually identified a marker for this process, a marker known as an 'apolypoprotein'. What we've seen that there's more of this marker in the rats that have had the stem cell graft, indicating that the cells themselves are participating in this active process of regeneration.

Is there a potential risk to patients of the stem cells going out of control once they've been transplanted?
What we're doing is generating a cell line that is a homogenous cell line, that we can test thoroughly prior to it going into the clinic, so it can be tested in the lab, it can be tested on animals, and then subsequently also be tested on a small patients groups in clinical trials. Clearly those cells are homogenous, they will not continue to grow once they've been transplanted, so there's no risk that the graft will overgrow and generate side effects.

How is your research applicable to treating age-related diseases?
Stem cells are actually with us throughout life, so literally they're the first things that we have that make us up, but also they persist, to a greater or lesser extent. But as we age we gradually lose our stem cells, because they're used up to repair a bit of damage here, to patch up a bit of damage there, and as we get older we have no stem cells within us that are able to repair any serious form of damage such as a stroke. However, it's almost certain now that our brain retains the capacity to deal with stem cells so if we inject them into our brains the signals are present to direct those stem cells to make the cells that have been lost in brain damage.

How will people benefit from the research that you are doing, and how soon will it be before these benefits are apparent?
The diseases that really prove to be the major drain on resources, both within the health service and with the social services, are the major degenerative diseases of the elderly, and the best examples of these are obviously stroke, Alzheimer's disease and Parkinson's disease. There are no really effective treatments for these conditions, particularly in the case where patients have had these diseases for a certain period of time - there are often some drugs that can be used in the early stages of the diseases, but these have a relatively limited life span in terms of keeping the patients well and retaining their independence.

What ReNeuron is seeking to do is to generate a variety of products that can be used where there are simply no other drugs available, that is in patients that have had these diseases for a length of time, where they're showing chronic disability, where their prognosis is poor. Here we can offer at least the hope that these patients would retain their independence and not be dependent entirely on the State or on the hospital system for their life.

Our first target is stroke, because there's a huge incidence of stroke in the elderly every year, most of the patients will survive that stroke and most of those patients that survive will have a chronic disability - inability to speak, inability to move an arm, to walk properly - and they will be seeking something that will help them. Our first cell line that we're developing now is a human cell line from the region of the brain that's affected in stroke, and we're actually selecting that cell line to go into banking at the moment. Certainly what we're talking about here is small scale trials, and there will be a long process that the regulators - the government agencies that approve the widespread use of medicine - will be involved in. Clearly it will take some time to convince them that this really very novel form of therapy is both safe and efficacious. So we don't expect that a product will be widely available for some years, and we're obviously going to be increasing the number of products that we hope to have available, so we're looking at products for Alzheimer's disease and Parkinson's disease as well.

We are also looking at different types of diseases that we believe would be amenable to stem cell therapy, including heart disease, where heart attack is obviously a major killer and the actual damage to the heart we believe could be repaired by a simple injection of stem cells. I think it's important to remember that this is a treatment that has not yet been used in human patients - the next major milestone in stem cell research is going to be testing the stem cells in humans. I think, nevertheless, companies like ourselves and scientists like myself are very confident that this is something that will move forward quite fast and once the initial proof of principle has been shown in humans then really the whole world is going to open up for a whole new set of treatments.

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Content last updated: 17/07/2006

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