Regenerative Medicine: S&T Committee Report

Baroness Greenfield Excerpts

Thursday 13th March 2014 Lords Chamber

[Baroness Greenfield (CB)]

I add my voice to those of the other noble Lords in congratulating the noble Lord, Lord Patel, on bringing attention to this timely and important report. He and others have already spoken eloquently on the wider issues surrounding stem cell research, so I shall restrict my comments to my own particular area: diseases of the central nervous system.

While other conditions such as heart disease and cancer are devastating, we all fear in particular the disorders that destroy our brains. The report discusses the wonderful prospect that in the next five years treatments are likely to be available for stroke and multiple sclerosis. However, only under a section on longer-term possibilities is Parkinson’s disease mentioned.

The neurodegenerative diseases of Alzheimer’s and Parkinson’s target the very essence of what it means to be human: what it means to move freely, to smile, to think, to speak and to have memories—indeed, to be a unique individual. The problem is that, as yet, we do not know why key brain areas in each case embark on the initial cycle of self-destruction or why it occurs only in certain brain regions and not in others. Because we do not currently understand the basic mechanisms, we cannot get to the root of the problem. The best that we can do is to combat the symptoms.

As brain cells die, they release less and less of their essential chemical messengers. Current strategies, therefore, are to offset the dwindling level of those naturally occurring chemicals with drugs, but here the problems are several-fold. First, as with all drugs, the treatment will permeate into areas of the brain and body where it is not needed and hence cause side-effects. For example, with Parkinson’s disease, treatment with the drug in current use, L-dopa, will supply the necessary chemical messenger, dopamine, to the area of devastation, but will also raise levels of the same chemical elsewhere in the brain, and this can often result in psychotic side-effects, with disturbing hallucinations. Even when such treatment offers temporary alleviation of the patient’s basic condition—or slowing down of the deterioration, as in the case of the anti-Alzheimer’s drug Aricept—it has proved hard to convince organisations such as NICE that the costs are worthwhile.

The situation is made even worse when we consider how many more of us are going to need such treatment in the future. Today, nearly a million people suffer from Alzheimer’s or Parkinson’s or both, and that number is expected to double by 2050. The total cost of caring for one person with dementia can be up to £30,000 per patient per year—plus the additional costs caused by loss of earnings.

Even more sobering, beyond the mere economics, is the human cost. For every person suffering from either Parkinson’s or Alzheimer’s, let us say there are 10 people who care about that individual. Hence, as the number in the UK reaches almost 2 million by the middle of this century, almost 20 million lives could be affected by those devastating disorders.

So there is a huge and growing need: a need that is currently unmet. Stem cell therapy offers an exciting and realistic alternative. The rationale is completely different from that of conventional treatments. The idea is not to treat the symptoms, but to harness regenerative biological mechanisms so that new cells are created. That would be a real cure. It would not be merely replacing the chemicals that are lost as a result of cell death, but actually replacing the neurons themselves.

Some cases of Parkinson’s disease have been successfully treated using human foetal cells; however, such tissue is hard to obtain, and the ideal would be switch to human embryonic stem cells. Those cells are derived from very early embryos, at the stage when the embryo is a microscopic ball just a few days old and consisting of only one to 200 cells. Not only are they immortal, they can produce every type of cell in the body. By introducing such cells into the appropriate environment within the brain, they will actually become the brain cells that have been lost.

There are, inevitably, potential downsides, As a neuroscientist, I am unable to comment with any authority on the ethical or financial issues, so I will restrict my caveats to technical issues. The first would be immune rejection of the new cells. However, that can be overcome by immunotolerising patients or even by immunosuppression. Such therapies have side-effects, but the risk-benefit ratio compared to that with conventional drugs is greatly shifted in favour of the positive.

A further problem is that stem cells could proliferate out of control in the brain and therefore become a tumour. However, to date, there is no clinical evidence that that has occurred with stem cell therapy and, in any event, it could be circumvented by biochemical chicanery—for example, manipulating stem cells so that they divide at a few degrees hotter than would normally be the case in the living brain.

Another issue is that implanted stem cells may produce excessive amounts of chemical messenger compared to normal levels. In principle, however, once stem cells have repopulated the brain, they should behave like their naturally occurring predecessors and release chemicals within the normal range as and when they are stimulated and interacting in their normal brain environment. In any event, conventional drugs already produce excessive amounts of chemical messenger, but that can be controlled by current treatments.

Finally, we must be careful not to conflate Parkinson’s and Alzheimer’s diseases. They are very different conditions and are differentially tractable to stem cell therapy. Parkinson’s disease is much more localised in the brain than Alzheimer’s, and therefore it will be much easier to locate where the stem cells should be placed. However, there is often a co-pathology—patients presenting with both Alzheimer’s and Parkinson’s diseases—so in these cases perhaps the alleviation of the movement symptoms of Parkinson’s may help in the patient’s quality of life, not least because we know that the better that people can move physically, the more that they can sustain a good blood supply to the brain.

There is now a growing body of evidence that physical exercise can enhance the natural growth of brain cells, a phenomenon known as neurogenesis, as well as the proliferation of blood vessels, therefore bringing more oxygen to the brain, which improves its functioning. There are even some claims that Alzheimer’s disease could be less prevalent in those who exercise routinely. So a treatment for patients suffering from both Alzheimer’s and Parkinson’s that enabled them to move more freely might in the long term be more generally beneficial.

Some might say that introducing the cells into the brain would be problematic, but the brain surgery required is modest. Modern stereotactic surgery is performed under local anaesthetic, with only a small hole made in the skull and a fine needle introduced—a bit like drilling for oil using precise three-dimensional co-ordinates. The area targeted can then be localised.

In summary, we have reason to be confident that, although not without risks or difficulties, stem cell therapy could be a chance to harness the nervous system’s natural mechanisms to regenerate itself. In the case of neurodegenerative disorders, though, much more research needs to be done.

I commend the authors of the report for increasing the chances that we will,

“facilitate the translation of scientific knowledge into clinical practice and encourage its commercial exploitation.”.

Still, far more money needs to be devoted to research into the use of stem cells in brain disease, which at present is a poor relation to heart disease and cancer. If these recommendations are implemented, the horizons could be very bright, not just for those with Alzheimer’s and Parkinson’s, who are currently condemned to a highly disabled life and an even bleaker future, but for everyone who cares about them.